Drug delivery device with proximity sensor

ABSTRACT

A drug delivery device, in the form of an injector, may include one of a number of systems for limiting the delivery of a medical fluid or drug product in case of movement of (e.g., removal of) the injector relative to the patient as determined by a proximity sensor. The drug delivery system may in the alternative or in addition include systems for indicating the amount of medical fluid or drug product delivered (or not delivered) in case of movement of (e.g., removal of) the injector relative to the patient as determined by the proximity sensor. The injector may be, for example, an on-body injector or an hand-held autoinjector.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of PCT/US2015/066597, filed Dec. 18, 2015, whichclaims priority to U.S. Provisional Patent Application No. 62/094,395,filed Dec. 19, 2014, the entire contents of each of which are herebyincorporated by reference.

FIELD OF THE DISCLOSURE

This disclosure is directed to a drug delivery device and, inparticular, to a drug delivery device that limits drug delivery inaccordance with the state of a proximity sensor.

BACKGROUND

Medical fluids and drug products (e.g., drugs) can be administered to apatient through the use of drug delivery devices, such as autoinjectorsor on-body injectors or infusers. These devices may replace deliverysystems using the combination of a syringe and a vial of the medicalfluid or drug product or a pre-filled syringe. Autoinjectors and on-bodyinjectors may be used to automate the needle or cannula insertion andthe drug delivery or administration process, thereby simplifying theprocess for certain patient groups or sub-groups for which use of thesyringe/vial combination or pre-filled syringe systems would bedisadvantageous, such as groups or sub-groups demonstratingphysiological or psychological impediment.

In some instances, after automated insertion of the needle or cannula,the autoinjectors and on-body injectors may continue to allow drug topass through the needle or cannula even though a component of the device(e.g., injector) has become detached from the patient and the needle orcannula no longer is inserted into the patient. This has severalconsequences. First, the patient does not receive the full dose of thedrug, which may have a negative effect on the patient. Second, thepatient may not be aware of the fact that the full dose of the drug hasnot been delivered, leaving the patient with the false impression thatthe entire dose has been delivered when it has not. Third, even if thepatient is aware of the fact that the full dose has not been delivered,the patient may be unable to determine just how much of the dose wasdelivered. Conversely, the patient may not be able to determine how muchof the dose was not delivered.

As set forth in more detail below, the present disclosure provides animproved drug delivery device embodying advantageous alternatives to theconventional devices and methods.

SUMMARY

According to an aspect of the disclosure, a drug delivery device caninclude a reservoir, a cannula, a drive, a lock, a housing and aproximity sensor. The reservoir can include a bore having a first endand a second end, and a plunger assembly including a plunger moveablewithin the bore between the first and second ends. The cannula can havean operational state wherein the cannula is connected in fluidcommunication with the reservoir. The drive can be coupled to theplunger assembly to move the plunger between the first and second ends.The lock can be configured to selectively limit movement of the plungerbetween the first and second ends of the reservoir The reservoir, thedrive, and the lock can be disposed at least partially within thehousing. The proximity sensor can be operably coupled to move relativeto the housing, and can have a first sensor state wherein the proximitysensor extends from the housing and a second sensor state wherein theproximity sensor is retracted toward the housing relative to the firstsensor state. The lock can limit movement of the plunger assembly whenthe proximity sensor is in the first sensor state.

According to a further aspect of the disclosure, a method of limitingthe delivery of a drug from a drug delivery device after the drugdelivery device is removed from a patient can be provided. The methodcan include (a) providing a drug delivery device, wherein the drugdelivery device can include a reservoir, a cannula, a drive, a lock, ahousing and a proximity sensor. The reservoir can include a bore havinga first end and a second end, and a plunger assembly including a plungermoveable within the bore between the first and second ends. The cannulacan have an operational state wherein the cannula is connected in fluidcommunication with the reservoir. The drive can be coupled to theplunger assembly for moving the plunger between the first and secondends. The lock can be configured to selectively limit movement of theplunger between the first and second ends of the reservoir. Thereservoir, the drive, and the lock can be disposed at least partiallywithin the housing. And the proximity sensor can be operably coupled tomove relative to the housing, and can have a first sensor state whereinthe proximity sensor extends from the housing and a second sensor statewherein the proximity sensor is retracted toward the housing relative tothe first sensor state. The lock can limit movement of the plungerassembly when the proximity sensor is in the first sensor state. Themethod can further include, (b) when the drug delivery device is removedfrom the patient, causing the proximity sensor to occupy the firstsensor state after having occupied the second sensor state. And, themethod can include, (c) transmitting information from the proximitysensor to the lock to indicate that the proximity sensor has moved tothe first sensor state. Finally, the sensor can include (d) causing thelock to limit movement of the plunger assembly upon receivinginformation that the proximity sensor is in the first sensor state.

According to another aspect of the present disclosure, a drug deliverydevice such as an injector can include a reservoir including a borehaving a first end and a second end, and a plunger assembly including aplunger moveable within the bore between the first and second ends, anda cannula having an operational state wherein the cannula is connectedin fluid communication with the reservoir. The injector also includes aspring coupled to the plunger assembly to move the plunger between thefirst and second ends, a lock selectively coupled to one of the plungerassembly and the spring to limit movement of the plunger between thefirst and second ends with the lock coupled to the one of the plungerassembly and the spring, a housing, the reservoir, spring, and lockdisposed within the housing, and a proximity sensor coupled to the lockand moveable relative to the housing, the proximity sensor having afirst sensor state wherein the proximity sensor extends fully from thehousing and a second sensor state wherein the proximity sensor isretracted toward the housing, the lock coupled to the one of the plungerassembly and the spring with the proximity sensor in the first sensorstate.

According to another aspect of the present disclosure, a drug deliverydevice such as an injector can include a reservoir including a borehaving a first end and a second end, and a plunger assembly including aplunger moveable within the bore between the first and second ends, anda cannula having an operational state wherein the cannula is connectedin fluid communication with the reservoir. The injector also includes agas source having an operational state wherein the gas source is influid communication with the plunger to move the plunger between thefirst and second ends, a lock comprising a vent selectively coupled tothe gas source to limit movement of the plunger between the first andsecond ends, a housing, the reservoir, gas source, and lock disposedwithin the housing, and a proximity sensor coupled to the lock andmoveable relative to the housing, the proximity sensor having a firstsensor state wherein the proximity sensor extends fully from the housingand a second sensor state wherein the proximity sensor is retractedtoward the housing, the vent coupled to the gas source with theproximity sensor in the first sensor state.

According to a further aspect of the present disclosure, a drug deliverydevice such as an injector can include a reservoir including a borehaving a first end and a second end, and a plunger assembly including aplunger moveable within the bore between the first and second ends, anda cannula having an operational state wherein the cannula is connectedin fluid communication with the reservoir. The injector also includes aspring coupled to the plunger assembly to move the plunger between thefirst and second ends, an indicator selectively mechanically coupled tothe plunger assembly, a housing, the reservoir, spring, and indicator atleast partially disposed within the housing, and a proximity sensorcoupled to the indicator and moveable relative to the housing, theproximity sensor having a first sensor state wherein the proximitysensor extends fully from the housing and a second sensor state whereinthe proximity sensor is retracted toward the housing, the indicatorcoupled to the plunger assembly with the proximity sensor in the secondsensor state and the indicator decoupled from the plunger assembly withthe proximity sensor in the first sensor state.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure will be more fully understood from the followingdescription taken in conjunction with the accompanying drawings. Some ofthe figures may have been simplified by the omission of selectedelements for the purpose of more clearly showing other elements. Suchomissions of elements in some figures are not necessarily indicative ofthe presence or absence of particular elements in any of the exemplaryembodiments, except as may be explicitly delineated in the correspondingwritten description. None of the drawings are necessarily to scale.

FIG. 1 is a cross-sectional view of an embodiment of a drug deliverydevice with a sliding lock that cooperates with a plunger arm and aproximity sensor in a first, off-body state;

FIG. 2 is a cross-sectional view of the embodiment of FIG. 1 taken alongline 2-2, with the proximity sensor in the first, off-body state;

FIG. 3 is a cross-sectional view of the embodiment of FIG. 1 taken alongline 2-2, with the proximity sensor in a second, on-body state;

FIG. 4 is a cross-sectional view of another embodiment of a drugdelivery device with a pivoting lock that cooperates with a plunger armand a proximity sensor in a first, off-body state;

FIG. 5 is a cross-sectional view of the embodiment of FIG. 4 taken alongline 5-5, with the proximity sensor in the first, off-body state;

FIG. 6 is a diagram relating the motion of the ends of the lever of theembodiment illustrated in FIGS. 4 and 5;

FIG. 7 is a cross-sectional view of an embodiment of a drug deliverydevice with a sliding lock that cooperates with a spring and a proximitysensor in a first, off-body state;

FIG. 8 is a cross-sectional view of the embodiment of FIG. 7 taken alongline 8-8, with the proximity sensor in a second, on-body state;

FIG. 9 is a cross-sectional view of an embodiment of a drug deliverydevice with a pivoting lock that cooperates with a spring and aproximity sensor in a first, off-body state;

FIG. 10 is a cross-sectional view of the embodiment of FIG. 9 takenalong line 10-10, with the proximity sensor in a second, on-body state;

FIG. 11 is a cross-sectional view of an embodiment of a drug deliverydevice with a lock including a vent and a proximity sensor in a second,on-body state;

FIG. 12 is a cross-sectional view of the embodiment of FIG. 11 with theproximity sensor in a first, off-body state;

FIG. 13 is a perspective view of an injector with a fluid deliveryindicator and a proximity sensor;

FIG. 14 is a partial cross-sectional view of the embodiment of FIG. 13in an off-body state;

FIG. 15 is a partial cross-sectional view of the embodiment of FIG. 13in the on-body state;

FIG. 16 is a perspective view of an on-body injector, which mayincorporate any one of the foregoing embodiments illustrated in FIGS.1-15;

FIG. 17 is a cross-sectional view of the on-body injector of FIG. 16;

FIG. 18 is a cross-sectional view of the on-body injector of FIG. 16;

FIG. 19 is a perspective view of an autoinjector, which may incorporateany one of the embodiments illustrated in FIGS. 1-15;

FIG. 20 is a cross-sectional view of the autoinjector of FIG. 19;

FIG. 21 is a cross-sectional view of an embodiment of a drug deliverydevice with a proximity sensor and lock including a movable plate in afirst, off-body state;

FIG. 22 is a cross-sectional view of the embodiment of FIG. 21 with theproximity sensor and lock in a second, on-body state;

FIG. 23 is a cross-section view of an alternative version of theauto-injector of FIGS. 19 and 20 including a needle assembly that servesas a proximity sensor; and

FIG. 24 is a side view of the needle assembly of FIG. 23.

GENERAL DESCRIPTION

A drug delivery device, in the form of an injector, may include varioussystems for limiting the delivery of a medical fluid or drug product incase of movement of (e.g., removal of) the injector relative to apatient as determined by a proximity sensor. The drug delivery systemmay in the alternative or in addition include systems for indicating theamount of medical fluid or drug product delivered (or not delivered) inthe case of movement of (e.g., removal of) the injector relative to thepatient as determined by the proximity sensor. The injector may be, forexample, an on-body injector or a hand-held autoinjector. The injectormay be used with one of a variety of medical fluids or drug products.

In one embodiment, an injector comprises a reservoir including a borehaving a first end and a second end, and a plunger assembly including aplunger moveable within the bore between the first and second ends. Theinjector further comprises a cannula having an operational state whereinthe cannula is connected in fluid communication with the reservoir, anda spring coupled to the plunger assembly to move the plunger between thefirst and second ends. The injector also comprises a lock selectivelycoupled to one of the plunger assembly and the spring to limit movementof the plunger between the first and second ends with the lock coupledto the one of the plunger assembly and the spring, a housing, thereservoir, spring, and lock disposed within the housing, and a proximitysensor coupled to the lock and moveable relative to the housing, theproximity sensor having a first sensor state wherein the proximitysensor extends fully from the housing and a second sensor state whereinthe proximity sensor is retracted toward the housing, the lock coupledto the one of the plunger assembly and the spring with the proximitysensor in the first sensor state.

According to another embodiment, the plunger assembly includes a plungerarm attached to the plunger, the lock has a wall that abuts the plungerarm to limit movement of the plunger when the lock is coupled to theplunger assembly, and the proximity sensor is coupled to the wall, wherethe wall abuts the plunger arm with the proximity sensor in the firstsensor state and the wall is spaced from the plunger arm with theproximity sensor in the second sensor state.

According to another embodiment, the plunger arm has at least oneshoulder formed thereon, and the wall abuts the at least one shoulder ofthe plunger arm to limit movement of the plunger when the lock iscoupled to the plunger assembly.

According to another embodiment, the injector further comprises a platedisposed at least partially within the housing and coupled to thehousing to translate relative to the plunger arm, the plate having afirst end that defines the wall of the lock and a second end thatdefines the proximity sensor.

According to another embodiment, the injector further comprises a leverhaving a first end disposed within the housing and defining the wall ofthe lock, and a second end disposable outside the housing and definingthe proximity sensor.

According to another embodiment, the lock has a wall that abuts thespring to limit movement of the plunger when the lock is coupled to thespring, and the proximity sensor is attached to the wall, where the wallabuts the spring with the proximity sensor in the first sensor state andthe wall is spaced from the spring with the proximity sensor in thesecond sensor state.

According to another embodiment, the injector further comprises a platedisposed at least partially within the housing and coupled to thehousing to translate relative to the spring, the plate having a firstend that defines the wall of the lock and a second end that defines theproximity sensor.

According to another embodiment, the injector further comprises a leverhaving a first end disposed within the housing and defining the wall ofthe lock, and a second end disposable outside the housing and definingthe proximity sensor.

According to another embodiment, the injector further comprises a springcoupled to the proximity sensor, the spring biasing the proximity sensortoward the first sensor state.

According to another embodiment, the lock is reversibly coupled to theone of the plunger assembly and the spring.

According to another embodiment, the lock is irreversibly coupled to theone of the plunger assembly and the spring.

According to another embodiment, the proximity sensor has a third sensorstate wherein the proximity sensor is retracted toward the housing, thelock being coupled to the one of the plunger assembly and the springwith the proximity sensor in the third sensor state, the lock beingreversibly coupled to the one of the plunger assembly and the springwith the sensor occupying the third sensor state subsequent to occupyingthe second sensor state, and the lock being irreversibly coupled to theone of the plunger assembly and the spring with the sensor occupying thefirst sensor state subsequent to occupying one of the second and thirdsensor states.

According to another embodiment, the lock prevents movement of theplunger between first and second ends with the lock coupled to the oneof the plunger assembly and the spring.

According to another embodiment, the lock limits movement of the plungerbetween first and second ends with the lock coupled to the one of theplunger assembly and the spring.

According to another embodiment, the injector is a hand-heldautoinjector, the injector comprising a needle shield that defines theproximity sensor.

According to another embodiment, the injector is an on-body injector,the injector comprising a surface having adhesive applied thereto toattach the injector to a body of a patient.

According to a further embodiment, an injector comprises a reservoirincluding a bore having a first end and a second end, and a plungerassembly including a plunger moveable within the bore between the firstand second ends, a cannula having an operational state wherein thecannula is connected in fluid communication with the reservoir, and agas source having an operational state wherein the gas source is influid communication with the plunger to move the plunger between thefirst and second ends. The injector further comprises a lock comprisinga vent selectively coupled to the gas source to limit movement of theplunger between the first and second ends, a housing, the reservoir, gassource, and lock disposed within the housing, and a proximity sensorcoupled to the lock and moveable relative to the housing, the proximitysensor having a first sensor state wherein the proximity sensor extendsfully from the housing and a second sensor state wherein the proximitysensor is retracted toward the housing, the vent coupled to the gassource with the proximity sensor in the first sensor state.

According to another embodiment, the gas source is a pressurizedcontainer of gas.

According to another embodiment, the gas source is a container of amaterial capable of a phase change from liquid to gas or solid to gas.

According to another embodiment, the vent comprises a seal.

According to another embodiment, the vent comprises a piercable septum.

According to a still further embodiment, an injector comprises areservoir including a bore having a first end and a second end, and aplunger assembly including a plunger moveable within the bore betweenthe first and second ends, a cannula having an operational state whereinthe cannula is connected in fluid communication with the reservoir, anda spring coupled to the plunger assembly to move the plunger between thefirst and second ends. The injector further comprises an indicatorselectively mechanically coupled to the plunger assembly, a housing, thereservoir, spring, and indicator at least partially disposed within thehousing, and a proximity sensor coupled to the indicator and moveablerelative to the housing, the proximity sensor having a first sensorstate wherein the proximity sensor extends fully from the housing and asecond sensor state wherein the proximity sensor is retracted toward thehousing, the indicator coupled to the plunger assembly with theproximity sensor in the second sensor state and the indicator decoupledfrom the plunger assembly with the proximity sensor in the first sensorstate.

According to another embodiment, the plunger assembly comprises aplunger arm attached to the plunger, the indicator being mechanicallycoupled to the plunger arm through a gear train having at least one gearthat is moveable into and out of engagement, and the proximity sensor iscoupled to the at least one gear to move the at least one gear out ofengagement and decouple the indicator from the plunger arm with theproximity sensor in the first sensor state.

DETAILED DESCRIPTION

Turning now to FIGS. 1-3, a drug delivery device such as an injector 100includes a reservoir 102, a plunger assembly 110, a cannula 114, and adrive 116. The reservoir 102 includes a bore 104 having a first end 106and a second end 108. The plunger assembly 110 includes a plunger 112moveable within the bore 104 of the reservoir 102 between the first andsecond ends 106, 108. The cannula 114 includes an operational statewherein the cannula 114 is connected in fluid communication with thereservoir 102. The drive 116, in the form of a spring, is coupled to theplunger assembly 110 to move the plunger 112 between the first andsecond ends 106, 108.

According to the embodiments illustrated in FIGS. 1-12, the injector 100is also provided with a lock 118 selectively coupled to one of theplunger assembly 110 and the drive 116 to limit movement of the plunger112 between the first and second ends 106, 108 of the bore 104. Forexample, the lock 118 may be coupled to the one of the plunger assembly110 and the spring 116. See, e.g., FIGS. 1-10. Another embodiment of thelock 118 is illustrated in FIGS. 11 and 12.

The injector 100 includes a proximity sensor 120 coupled to the lock 118and moveable relative to a housing 122 in which the reservoir 102,spring 116, and lock 118 are disposed. The proximity sensor 120 has afirst sensor state (or position) wherein the proximity sensor 120extends (e.g., extends fully) from the housing 122 (see, e.g., FIGS. 1and 2) and a second sensor state (or position) wherein the proximitysensor 120 is retracted toward and into the housing 122 relative to thefirst sensor state (see, e.g., FIG. 3). The lock 118 is coupled to theone of the plunger assembly 110 and the spring 116 with the proximitysensor 120 in the first sensor state so as to limit or prevent movementof the plunger 112.

In certain embodiments, the reservoir 102 may be in the form of apre-filled syringe, in which case the cannula 114 may be in the form ofa needle fixedly or securely attached to a hub 130 at the second end 108of the reservoir 102. See, FIG. 1. According to other embodiments, thereservoir 102 may be pre-filled, but the cannula 114 may be moveablerelative to the hub 130 of the reservoir 102. In some embodiments, thehub 130 can include a septum such that the cannula 114 can be moved inthe direction of the hub 130 to pierce the septum in the operationalstate. In certain embodiments, an assembly may be disposed between thecannula 114 and the hub 130 to dispose the cannula 114 into fluidconnection with the hub 130 in the operational state, which assembly mayalso insert the cannula 114 into the patient. In some embodiments, abarrier may be disposed about the end of the cannula 114 that piercesthe septum to preserve the sterility at the junction between the cannula114 and the septum. In some embodiments, the cannula 114 either may befixedly or securely attached or may be moveable relative to thereservoir 102 (more particularly, the hub 130), but the reservoir 102may not be pre-filled.

As illustrated in FIG. 1, the plunger assembly 110 may include a plungerarm 140 attached to the plunger 112. The lock 118 has a wall 142 thatabuts the plunger arm 140 to limit movement of the plunger 112 when thelock 118 is coupled to the plunger assembly 110. The proximity sensor120 is coupled to the wall 142 (as illustrated, the sensor 120 isintegral, or one piece, with the wall 142), such that the wall 142 abutsthe plunger arm 140 with the proximity sensor 120 in the first sensorstate (FIGS. 1 and 2) and the wall 142 is spaced from the plunger arm140 with the proximity sensor 120 in the second sensor state (FIG. 3).

In some embodiments, the plunger arm 140 may have at least one shoulder144 (FIG. 1) formed thereon, and the wall 142 abuts the at least oneshoulder 144 of the plunger arm 140 to limit and/or prevent movement ofthe plunger 112 when the lock 118 is coupled to the plunger assembly110. As illustrated in FIG. 1, the plunger arm 140 has a section of itslength (i.e., a dimension of the plunger arm 140 extending in adirection along a longitudinal axis 148 of the plunger arm 140) that hasat least one feature 150 that defines the at least one shoulder 144. Forexample, the plunger arm 140 may include a shaft 152 to which isattached one or more features 150 that include protrusions 154 (e.g.,teeth). In some embodiments, the protrusions 154 can be formedintegrally (as one piece) with the shaft 152. Spaces or notches 156between adjacent protrusions 154 permit the wall 142 to be disposedbetween adjacent protrusions 154, with the protrusion 154 positionedfurthest longitudinally from the plunger 112 defining the shoulder 144along a surface of the protrusion 154 that extends perpendicularly tothe axis 148. It will be recognized that the features 150 of theembodiment illustrated in FIGS. 1-3 may also be described as one or morespaces or notches 156 formed in the plunger arm 140, the spaces ornotches 156 being bounded by the material of the plunger arm 140previously described as shaft 152 and protrusions 154. These areequivalent descriptions for the disclosed subject matter.

As noted above, the lock 118 includes a wall 142 that fits in the spacesor notches 156 thereby coupling the lock 118 to the plunger assembly110. According to the embodiment illustrated in FIGS. 1-3, the injector100 includes a plate 158 disposed at least partially within the housing122 and coupled to the housing 122 to translate relative to the plungerarm 140. The plate 158 may have a first end 160 that defines the wall142 of the lock 118 and a second end 162 that defines the proximitysensor 120. See FIGS. 2 and 3. While the wall 142 has been described asbeing part of the plate 158, which is depicted in FIGS. 2 and 3, forexample, as a generally planar structure, this is merely an example. Thewall 142 of the lock 118 could also be defined by part of a pin, a fork,or any other component not expressly depicted but capable of serving theintended purpose.

In some embodiments, the injector 100 may include a spring 166 coupledto the proximity sensor 120 (via the plate 158), the spring 166 biasingthe proximity sensor 120 (again, via the plate 158) toward the firstsensor state. In certain embodiments, the second end 160 may include aguide 172 about which the spring 166 is disposed, a first end 174 of thespring 166 abutting a shoulder 176 of the plate 158 and a second end 178abutting an interior surface 180 of the housing 122. While a coil spring166 is illustrated, any of a number of different biasing elements may beused, which biasing elements may bias the first end 162 of the plate 158outwardly from the housing 122.

In some embodiments, the injector 100 may include guides attached to thehousing 122 that prevent the plate 158 from other than translationalmovement along a line of motion 182. For example, a guide may bedisposed on either side of the plate (i.e., to the right or the left ofthe plate 158 as illustrated in FIG. 2) to prevent lateral movementrelative to the line of motion 182.

Disposed between the first and second ends 160, 162 of the plate 158 isan aperture 184. While the aperture 184 appears to be closer to thesecond end 160 of the plate 158 than the first end 162, otherarrangements are possible. Furthermore, while the aperture 184 appearsto be fully surrounded by the plate 158, such that the entirecircumference of the aperture 184 is defined by the plate 158, it isalso possible that at least a section of the aperture 184 is notsurrounded by the plate 158 and thus the plate 158 only partiallydefines the circumference of the aperture 184. Furthermore, while thecircumference of the aperture 184 appears oblong or keyhole in shape inFIG. 2, the aperture 184 is not limited to any particular shape.

As illustrated in FIGS. 1 and 2, when the injector 100 is not disposedon the surface of the patient's skin, the proximity sensor 120 extendsfrom the housing 122 as a consequence of the force applied to the plate158 by the spring 166. See FIG. 2. In turn, the plate 158 is positionedrelative to the plunger assembly 110, and in particular the plunger arm140, such that the plate 158 resides within one of the spaces or notches156. Compare FIGS. 1 and 2. When the injector 100 is disposed on thesurface of the patient's skin, the proximity sensor 120 is moved intothe housing 122 against the bias of the spring 166. As a consequence,the plate 158 is moved into a position where the aperture 184 is alignedwith the plunger arm 140, such that the plate 158 no longer resideswithin one of the spaces or notches 156. See FIG. 3. This permitsmovement of the plunger arm 140 and associated plunger 112 as aconsequence of the force applied to the plunger arm 140 by the spring116.

During the motion of the plunger arm 140 toward the right relative tothe orientation of FIG. 1, the injector 100 may become detached ordisplaced from the patient's skin. In such a case, the plate 158 wouldbe permitted to move under bias of the spring 166 such that the aperture184 is no longer aligned with the plunger arm 140, and instead the plate158 becomes disposed within one of the spaces or notches 156. In thisversion, the spring 166 transmits information to the lock 118 in theform of a mechanical force indicative of the position of the plate 158and proximity sensor 120. This force can cause engagement between theplate 158 and one of the protrusions 154 that would prevent furthermotion of the plunger arm 140 at the urging of the spring 116, and wouldlimit the amount of medical fluid or drug product ejected from thereservoir 102. That is, according to certain embodiments, engagementbetween the plate 158 and a protrusion may prevent any further medicalfluid or drug product from passing through and out of the cannula 114.According to other embodiments, the plunger arm 140 and associatedplunger 112 may travel some distance after the plate 158 becomesdisposed within a space or notch 156 but before the plate 158 engages aprotrusion 154, such that a limited amount of medical fluid or drugproduct may pass out of the reservoir through the cannula 114 even afteractivation of the lock 118. It will be recognized that by limiting theamount of medical fluid or drug product ejected from the reservoir 102,while arresting the overall motion of the plunger 112, significantadvantages may still be obtained.

It is not necessary that the lock 118 and proximity sensor 120 bedefined by a translating plate, such as is illustrated in FIGS. 1-3. Theembodiment illustrated in FIGS. 4 and 5 includes a different structurethat defines both a lock 118 and a proximity sensor 120. Because many ofthe structures of the embodiment of the injector illustrated in FIGS. 4and 5 are identical to those of the embodiment of FIGS. 1-3, likeelements have like reference numerals.

The structure of the embodiment illustrated in FIGS. 4 and 5 thatdefines both the lock 118 and the proximity sensor 120 is a lever 190.As shown in FIG. 5, the lever 190 has a first end 192 disposed withinthe housing 122 and defining the wall 142 of the lock 118, and a secondend 194 disposable outside the housing 122 and defining the proximitysensor 120. Disposed between the first and second ends 192, 194 is apivot 196 that may be attached to the housing 122.

The injector 100 may include a spring 198 coupled to the proximitysensor 120, the spring 198 biasing the proximity sensor 120 (lever 190)toward the first sensor state with the sensor 120 extending from thehousing 120. As illustrated, the spring 198 is a torsion spring that isdisposed at the pivot 196 and that applies a force to the lever 190 toone or the other side of the lever 190 to bias the lever 190, and thusthe sensor 120, toward the first sensor state (i.e., in a clockwisedirection relative to the orientation of FIG. 5). It will be recognizedthat other biasing elements may be used instead. For example, acompression spring may be disposed between the first end 192 of thelever 190 and the housing 122 to urge the lever 190, and thus the sensor120, toward the first sensor state.

Some change in orientation of the elements of the injector 100 may berequired to utilize the lever 190. Because the motion of the second end194 of the lever 190 into the housing 122 causes the first end 192 tomove counter-clockwise, the orientation of the plunger arm 140, and thespaces or notches 156 on the plunger arm 140, may be the reverse of thatillustrated in the embodiment of FIGS. 1-3. The spaces or notches 156may be positioned below the plunger arm 140, as depicted in FIG. 4. Inthis fashion, movement of the lever 190 caused by the motion of thesecond end 194 upon application of the injector 100 to the patient'sskin would cause the first end 192 to move away from the plunger arm 140and out of its respective space or notch 156. And upon removal of theinjector 100 from the patient's skin, whether deliberate or not, thespring 198 would cause the first end 192 of the lever 190 to move towardthe plunger arm 140 and into a respective space or notch 156 to lock thedevice. In this version, the spring 198 transmits information to thelock 118 in the form of a mechanical force indicative of the position ofthe lever 190 and thus the proximity sensor 120.

One advantage of the lever 190 is that it can permit a magnification ofthe travel of the second end 194, which in turn can increase thesensitivity of the proximity sensor 120. In particular, as illustratedin FIG. 6, the second end 194 moves a distance d relative to the surfaceof the housing 122 (for purposes of this discussion, this surface isalso the patient contact surface). The first end 192 in turn moves adistance D relative to the same surface of the housing 122. Thesedistances (d, D) are related to a length L of the lever 190, a length lof the lever 190 to the second end 194 and the offset H of the pivot 196relative to the surface of the housing 122. If the length l is one-thirdof the length L, then changes in the distance d will result in changesapproximately twice as large for the distance D (assuming a relativelysmall offset H). As long as length l is less than half of length L, anincreased sensitivity to motion will be realized.

The sensitivity of the embodiment utilizing a lever 190 may also beinfluenced by changes in the shape of the lever 190. The lever 190illustrated in FIGS. 4-6 is relatively straight. Alternatively, thelever 190 may be shaped with a bend between the two ends 192, 194 tochange the relationship between the movement of the second end 194 tothe first end 192.

While the embodiments of FIGS. 1-3 and 4-6 have been illustrated with asingle structure (plate 158, lever 190) defining both the lock 118 andthe proximity sensor 120, other embodiments may not be so limited. Forexample, both the lock 118 and the sensor 120 may each be defined by atranslating plate, similar to the plate 158, except that the first platethat defines the lock 118 may be disposed in a first region of theinjector 100 and the second plate that defines the sensor 120 may bedisposed in a second region of the injector 100 spatially removed fromthe first region. The second plate that defines the sensor 120 may becoupled to the first plate that the defines the lock 118 by a lever orother mechanical system disposed within the housing. A pivot for thelever coupling the sensor 120 to the lock 118 may be selected to providegreater sensitivity that may be possible if a single structure definedboth lock 118 and sensor 120. In addition, a lever may permit the sensor120 to be disposed closer to the cannula 114 while the lock 118 isdisposed proximate to the plunger arm 140, because the lock 118 and thesensor 120 are not defined by a single structure.

In further embodiments, other structures or assemblies of structures maybe used to transform motion of the sensor 120 into motion of the lock118. The foregoing example is simply one possible embodiment of a classof embodiments, individual examples of which may permit greatersensitivity while not necessarily permitting the lock 118 and the sensor120 to be disposed in spatially remote sections of the injector, andvice versa. Further, embodiments may provide other functions in additionor in substitution for those previously mentioned. For example, anintermediate structure or assembly may couple a sensor 120 moving in afirst direction to a lock 118 moving in a second direction, whichdirection may be different from the first (i.e., the sensor 120 maytravel along a first line of motion while the lock 118 moves along asecond line of motion that is at right angles to the first line ofmotion).

As noted above, the lock 118 may be coupled to one of the plungerassembly 110 and the spring 116. As illustrated in FIGS. 7-10, the lock118 may be coupled to the spring 116 instead of the plunger assembly110.

According to this embodiment, the plunger assembly 110 may or may notinclude a plunger arm 140. As illustrated in FIGS. 7-10, the plungerassembly 110 does not include a plunger arm 140, but the spring 116 actsdirectly against the plunger 112, the force applied by the spring 116causing motion of the plunger 112. It will be recognized that theembodiments of the lock 118 described below would work equally as wellif the spring 116 applied its force to an intermediate structure, suchas a plunger arm 140, instead of directly to the plunger 112.

According to the embodiment illustrated in FIG. 7, the lock 118 has awall 200 that abuts the spring 116 to limit movement of the plunger 112when the lock 118 is coupled to the spring 116. In some embodiments, asillustrated, the spring 116 may be a coil spring, and the wall 200 maybe disposed between adjacent coils 202 of the spring 116 to limit theforce applied to the plunger 112. The proximity sensor 120 is attachedto the wall 200, and the wall 200 abuts the spring 116 with theproximity sensor 120 in the first sensor state and the wall 200 isspaced from the spring 116 with the proximity sensor 120 in the secondsensor state. In some embodiments, the injector may include a spring 204coupled to the proximity sensor 120, the spring 204 biasing theproximity sensor 120 toward the first sensor state.

The embodiment illustrated in FIGS. 7 and 8 may include a plate 206 thatdefines the wall 200. The plate 206 may be disposed at least partiallywithin the housing 122 and coupled to the housing 122 to translaterelative to the spring 116. The plate 206 may have a first end 208 thatdefines the wall 200 of the lock 118 and a second end 210 that definesthe proximity sensor 120. In some embodiments, the plate 206 includes anaperture 212 that is sized such that the spring 116 may pass through theplate 206 when the sensor 120 is in the second sensor state, theconsequence of which would be for the spring 116 to move freely withoutinterference from the plate 206 and exert a force against the plunger112.

The discussion relative to the operation and configuration of the plate158 relative to the plunger arm 140 applies with equal force relative tothe operation and configuration of the plate 206 relative to the spring116. For example, like the version in FIGS. 1-3, when the injector 100in FIGS. 7 and 8 is removed from the patient, the spring 204 transmitsinformation to the plate 206 of the lock 118 in the form of a mechanicalforce indicative of the position of the proximity sensor 120.

In some embodiments, the injector may include a lever 220, asillustrated in FIGS. 9 and 10, in substitution for the plate 206. Asshown in FIG. 10, the lever 220 may have a first end 222 disposed withinthe housing 122 and defining the wall 200 of the lock 118. The lever 220may also have a second end 224 disposable outside the housing 122 anddefining the proximity sensor 120. This injector may also include aspring 228 coupled to the proximity sensor 120, the spring 228 biasingthe proximity sensor 120 (lever 220) toward the first sensor state. Forexample, the spring 228 may be a torsion spring.

The discussion relative to the operation and configuration of the lever190 relative to the plunger arm 140 applies with equal force relative tothe operation and configuration of the lever 220 relative to the spring116. For example, like the version in FIGS. 4-6, when the injector 100in FIGS. 9 and 10 is removed from the patient, the spring 228 transmitsinformation to the wall 200 of the lock 118 in the form of a mechanicalforce indicative of the position of the lever 220 and proximity sensor120. In addition, the discussion above relative to the lock 118 and thesensor 120 being defined by a single structure or by separate structurescoupled by one or more intermediate structures or assemblies ofstructures applies with equal force regarding the embodimentsillustrated in FIGS. 7-10 as it did relative to the embodimentsillustrated in FIGS. 1-6.

According to some embodiments, the lock 118 may be reversibly coupled tothe one of the plunger assembly 110 and the spring 116. For example, ifthe injector 100 is removed from the patient's skin duringadministration, the lock 118 would limit or prevent furtheradministration of the medical fluid or drug product. But, in embodimentswhere the lock 118 is reversible, the lock 118 may be unlocked, ordecoupled, if the proximity sensor 120 determines that the injector 100has been replaced against the patient's skin. In other embodiments, thelock 118 may be irreversibly coupled to the one of the plunger assembly110 and the spring 116. Such embodiments would prevent the injector 100from operating even if the injector 100 was re-positioned against thepatient's skin. In some embodiments, the decision to make the lock 118reversible or irreversible may be selected by the patient or caregiverusing the delivery device.

One example of an irreversible lock 118 is illustrated in FIG. 1,wherein all but one of the features 150 extending up from the plungerarm 140 can include transverse teeth 151 extending into spaces ornotches 156 between the features 150. In the version of FIG. 1, all ofthe features 150 include a tooth 151 except for the feature 150 locatedin closest proximity to the plunger 112. So configured, before theinjector 100 is ever operated, the lock 118 resides in the space ornotch 156 disposed between the plunger 112 and the adjacent toothlessfeature 150. Upon the injector 100 being positioned against a patient'sskin, the proximity sensor 120 and lock 118 move into the injector 100to allow the plunger assembly 110 to drive the plunger 112 andadminister drug to the patient. This causes the plunger arm 140 to moveto the right relative to the orientation of FIG. 1. Then, once theinjector 100 is removed from the patient's skin, the spring 166 biasesthe lock 118 and proximity sensor 120 back out of the injector 100 andinto the position illustrated in FIG. 1, for example. Here, the lock 118would be positioned in a space or notch 156 between two features 150,one of which includes a tooth 151. The tooth 151 resides above the lock118, or in a recess formed in the lock 118, for example, such that abottom surface of the tooth 151 engages an upward facing surface of thelock 118, thereby preventing the lock 118 and proximity sensor 120 frommoving back up into the injector 100. While FIG. 1 illustrates thefeatures 150 as having the teeth 151, this would only apply to thoseinjectors 100 where the lock 118 is irreversible. For a reversible lock118, the injector 100 would not include the teeth 151.

Some embodiments of the injector 100 may have a lock 118 that isreversibly coupled and irreversibly coupled to one of the plungerassembly 110 and the spring 116 according to the state of the proximitysensor 120. For example, the proximity sensor 120 may have a thirdsensor state wherein the proximity sensor 120 is retracted toward thehousing relative to the first sensor state but not as far as the secondsensor state. In some embodiments, the third sensor state can beconsidered an intermediate state between the first and second sensorstates. With the proximity sensor 120 in the third sensor state, thelock 118 can be coupled to the one of the plunger assembly 110 and thespring 116 to limit or prevent further movement of the plunger 112.Further, the lock 118 may be reversibly coupled to the one of theplunger assembly 110 and the spring 116 with the proximity sensor 120 inthe third sensor state subsequent to occupying the second sensor state.And, the lock 118 can be irreversibly coupled to the one of the plungerassembly 110 and the spring 116 with the proximity sensor 120 in thefirst sensor state subsequent to occupying one of the second and thirdsensor states.

To illustrate the foregoing, consider the following example. A patientapplies the device to his or her skin. As a consequence, the proximitysensor 120 is disposed wholly or partially in the housing 120. As afurther consequence, the lock 118 is disengaged or uncoupled from theplunger assembly 110 or the spring 116, and the device begins injectingthe medical fluid or drug product into the patient.

At a time thereafter, but before the full dose has been administered,the delivery device may be disturbed, causing a separation of the devicefrom the patient's skin, as determined by the proximity sensor 120. Thisdisturbance may cause the cannula 114 to only shallowly penetrate thepatient's skin, but may not separate the injector 100 from the patient'sskin to such a degree that the cannula 114 is completely removed or thesterility of the access site is compromised. In such a circumstance, thedelivery of the medical fluid or drug product may be interrupted by thecoupling of the lock 118 with the plunger assembly 110 or the spring 116to prevent medical fluid or drug product leakage that may occur becauseof shallow cannula 114 penetration. But, this coupling is reversible sothat an application of force that moves the cannula 114 back to itsproper depth, as determined by the proximity sensor 120, will cause thelock 118 to decouple from the plunger assembly 110 or spring 116,thereby re-starting administration of the medical fluid or drug product.

By having a reversible coupling, the medical fluid or drug productremaining in the reservoir 102 can be successfully delivered and wouldnot end up being treated as waste. Consequently, reversible coupling ofthe lock 118 to the plunger assembly 110 or the spring 116 would providean opportunity to save a dose in the event of a minor disturbance or useerror. Additionally, this may provide a higher success rate onchallenging anatomies by allowing applied pressure to fix or correct an“error” state and permit delivery to resume.

If, however, the delivery device becomes disturbed to such a degree thatthe cannula 114 is completely removed from the patient (for example, thedevice falls completely off the patient) before the full dose has beenadministered, then it may be undesirable to permit the patient orcaregiver to reapply the injector 100 to the patient. Consequently, toreduce the likelihood that the patient or caregiver would attempt toreapply the injector 100, the lock 118 may irreversibly couple to theplunger assembly 110 or spring 116 to prevent the injector 100 from anyfurther drug delivery.

To illustrate this concept, consider an embodiment where insertion ofthe cannula 114 to a depth of 6 mm is preferred and a depth of 3 mm doesnot cause significant leakage—the 3 mm depth may be referred to as adelivery continuation threshold, and may represent the point, degree orlevel under which continued delivery presents an unacceptable risk ofleakage or improper administration. When the injector 100 is applied andthe proximity sensor 120 is in its fully retracted state, this maycorrespond to a state for the cannula 114 where the cannula 114 isinserted to a depth of 6 mm. If the injector 100 is disturbed, and thesensor 120 moves to a state where it is not fully retracted or fullyextended corresponding to a cannula depth of 3 mm (e.g., the sensor 120extends 3 mm from the housing 122), then the injector 100 may permitcontinued injection of the medical fluid or drug product. However, ifthe sensor 120 moves to a state corresponding to cannula depth of 2 mm(e.g., the sensor 120 extends 4 mm from the housing 122), then theinjector 100 may reversibly limit injection of the medical fluid or drugproduct by reversibly coupling the lock 118 to one of the plungerassembly 110 and the spring 116. If the sensor 120 then moves back to astate corresponding to a cannula depth of 3 mm (e.g., the sensor 120extends 3 mm from the housing 122) or more, then the injection mayresume.

However, if the sensor 120 moves to a state corresponding to a cannuladepth of 0 mm (e.g., the sensor 120 extends 6 mm from the housing 122),then the injection would be permanently and irreversibly limited throughthe irreversible coupling of the lock 118 to the plunger assembly 110 orspring 116. A depth of 0 mm may be referred to as a device removalthreshold, and may represent the point, degree or level at which thedevice has likely been compromised, removed or the cannula 114 disturbedsuch that further delivery/reapplication is undesirable or unsafe. Asimilar outcome may result where the cannula depth is not 0 mm, but somenon-zero value (e.g., 1 mm). A non-zero value may be selected becauseeven if the cannula 114 does not come completely out of the patient'sskin, this may still be considered to present an unacceptable risk.Alternatively, a non-zero value may be selected so that it is not arequirement that the sensor 120 determine complete separation tofail-safe in case of a false negative for complete separation (e.g.,partial interference between the housing 122 and the sensor 120).

The specifics of any particular embodiment may be influenced by, forexample, the distance to which the proximity sensor 120 extends from thehousing 120, the length of the cannula 114, the desired depth of theinsertion of the cannula 114 into the patient, and the relationshipbetween the depth of cannula insertion to the degree of leakage from theaccess site.

According to any of the foregoing embodiments, the lock 118 may limitmovement of the plunger 112 between first and second ends 106, 108 so asto completely prevent movement of the plunger 112 between the first andsecond ends 106, 108 upon the lock 118 being coupled to the one of theplunger assembly 110 and the spring 116. Alternatively, according to anyof the foregoing embodiments, the lock 118 may only limit movement ofthe plunger 112 between first and second ends 106, 108 withoutcompletely preventing movement of the plunger 112 between the first andsecond ends 106, 108 upon the lock 118 being coupled to the one of theplunger assembly 110 and the spring 116. That is, it is not arequirement of all embodiments that the engagement or coupling of thelock 118 immediately result in the complete cessation of movement of theplunger 112. In certain circumstances, the plunger 112 may continue itsmovement over a limited length of travel after activating the lock 118.The specific distance that the plunger 112 may travel may be known andpredetermined, as a consequence of the structure and operation of thelock 118, or the distance may be approximated based on the structure andoperation of the lock 118 or the tolerances in the manufacture of theinjector 100. In some embodiments, any limited length of travel of theplunger 112 that is allowed after engagement or coupling of the lock 118can occur, for example, because of the geometry of the wall 142 thatforms the lock 118 and the spaces or notches 156 on the plunger arm 140.That is, in some embodiments, the spaces or notches 156 may have adimension that is greater than a thickness or width of the wall 142. Assuch, it is foreseeable that in some embodiments, the plunger 112 cancontinue to move to the extent that the spaces or notches 156 are wider,even after the lock 118 has been engaged or coupled.

Those embodiments described above wherein the lock 118 engages orcouples to the plunger assembly 110, and in particular the plunger arm140, may be used with embodiments of an injector 100 wherein the drive116 is not in the form of a spring. For example, any device that acts onthe plunger arm 140 may be used as a drive 116 in the circumstancewherein the lock 118 engages or couples to the plunger assembly 110 tolimit the injection of medical fluid or drug product from the injector100. Where the drive 116 is not in the form of a spring, otherconsiderations may be required when the injection is limited byinteraction between the lock 118 and the drive 116.

According to another group of embodiments illustrated in FIGS. 11 and12, the injector includes a reservoir 102 including a bore 104 having afirst end 106 and a second end 108, and a plunger assembly 110 includinga plunger 112 moveable within the bore 104 between the first and secondends 106, 108. The injector 100 also includes a cannula 114 having anoperational state wherein the cannula 114 is connected in fluidcommunication with the reservoir 102.

Embodiments of the injector 100 illustrated in FIGS. 11 and 12 include adrive 116 in the form of a gas source 250 having an operational statewherein the gas source is in fluid communication with the plunger 112 tomove the plunger 112 between the first and second ends 106, 108. The gassource 250 may be a container of pressurized gas. In some embodiments,the gas source 250 may be a container of a material capable of a phasechange from liquid to gas or solid to gas. When activated, the gassource 250 applies positive pressure on the plunger 112 of the plungerassembly 110. In some embodiments, the gas source 250 can include afrangible seal (similar to that on a convention CO₂ cartridge) that ispunctured by a movable needle, for example, upon activation of theinjector 100. The movable needle may be operably connected to theproximity sensor 120 such that movement of the proximity sensor 120automatically moves the needle to puncture the frangible seal andactivate the gas source 250. In other embodiments, the injector 100 mayinclude a separate button operably connected to the movable needle suchthat a user of the injector 100 must depress the button to move theneedle and break the frangible seal on the gas source 250. In stillother embodiments, the injector 100 can include a mechanical orelectro-mechanical valve that opens and activates the gas source 250upon activation of the injector 100, or some other structure capable ofachieving the intended objective.

The injector 100 according to such an embodiment includes a lock 118comprising a vent 252 selectively coupled to the gas source 250 to limitor prevent movement of the plunger 112 between the first and second ends106, 108. When the vent 252 is opened, positive pressure from the gassource 250 can exhaust through the vent 252 instead of applying a forceagainst the plunger 112 of the plunger assembly 110. The vent 252 couldbe provided by a number of different mechanisms, and may be dependentupon the manner in which the positive pressure is delivered to theplunger 112. For example, the vent 252 could be defined by a rupturablewall or a moveable seal, which could provide an irreversible or areversible lock. According to one embodiment, the vent 252 may be in theform of a duck-bill valve.

Additionally, when the gas source 250 and vent 252 have a frangible sealor rupturable wall, the injector 100 could be considered as having an“irreversible” lock. For example, when the gas source 250 and vent 252are opened, the vent 252 limits or prevents the positive gas pressurefrom being applied against the plunger assembly 110. In such anassembly, the open “vent” causes the lock to operate irreversiblybecause there is only a single pressure source (i.e., the gas source250), and once its seal is broken, its contents will be expelled untilit is empty, especially if a seal of the vent 252 is also broken.Therefore, if the injector 100 is removed from the patient prematurely,the gas source 250 continues to expel gas which is then exhausted out ofthe vent 252. Any subsequent attempt to re-administer will fail if thegas source 250 is spent.

In some embodiments, the vent 252 may include a seal 254, such as apiercable septum or a duck-bill valve, and a vent cannula 256. The ventcannula 256 pierces the seal 254 to provide an exhaust pathway out ofthe vent 252. The reservoir 102, gas source 250, and lock 118 may bedisposed within the housing 122, while the proximity sensor 120 may bedisposed in whole or in part outside of the housing 122.

According to some embodiments, the proximity sensor 120 is coupled tothe lock 118 and moveable relative to the housing 122. The proximitysensor 120 has a first sensor state wherein the proximity sensor 120extends (e.g., extends fully) from the housing 122 and a second sensorstate wherein the proximity sensor 120 is retracted toward and into thehousing 122 relative to the first sensor state. The vent 252 is coupledto the gas source 250 with the proximity sensor 120 in the first sensorstate.

The injector 100 illustrated in FIGS. 11 and 12 includes a chamber 258that connects the gas source 250 with the reservoir 102. The vent 252 isdisposed in a wall of the chamber 258. The vent cannula 256, which maybe in the form of a blunt, open-ended needle, is attached to a first end260 of a vent lever 262. The second end 264 of the vent lever 262 iscoupled to the proximity sensor 120, which may be in the form ofcup-shaped button 266 that extends through an aperture 268 in a wall ofthe housing 122. Movement of the button 266 is transmitted by the ventlever 262 to the vent cannula 256.

The proximity sensor 120, and in particular the button 266, is biasedoutwardly from the housing 122 by a spring 274. The spring 274 may bedisposed between a support 276 and the second end 264 of the vent lever262, the button 266 being disposed opposite the support 276 relative tothe end 264 of the vent lever 262.

In operation, with the proximity sensor 120 extended (see FIG. 12) andthe gas source 250 not yet activated, the vent cannula 256 engages theseal 254 to exhaust the chamber 258. Because the gas source 250 has notyet been activated, there is no effect on the movement of the plunger112. However, once the proximity sensor 120 retracts into the housing122, the vent cannula 256 is moved so that the vent cannula 256 nolonger interrupts the seal 254 and a positive pressure may be generatedin the chamber 258 by the gas source 250. If the proximity sensor 120extends before the full dose is administered, such as by removal of theinjector 100 from the patient, the spring 274 biases the vent lever 262such that the vent cannula 256 is moved into engagement with the seal254, and the positive pressure in the chamber 258 is exhausted throughthe vent cannula 256. This decreases the pressure in the chamber 258,causing the movement of the plunger 112 to be limited, or even stopped.In this configuration, the spring 274 transmits information to the lock118, and specifically the vent lever 262 and vent cannula 256, in theform of a mechanical force indicative of the position of the vent lever262 and the proximity sensor 120.

The embodiment provided in FIGS. 11 and 12 is intended to be an exampleonly. Other structures may be substituted for the seal 254, vent cannula256, and vent lever 262. While a chamber 258 has been provided incommunication with the reservoir 102 and the gas source 250, the chamber258 may not be present in other embodiments. Additionally, in someembodiments, the cannula 114 may be an open ended needle that allowsflow, as depicted in FIGS. 11 and 12, or it could just be anything thatwhen wedged into the seal 254 prevents sealing. As such, the cannula 114could include a thin solid rod to create a flow path around itself wherethe seal is poor, or a square profile might encourage even more flow. Anopen ended needle as depicted might be useful for puncturing a septum,for example, since a septum could be designed to reseal around theperimeter of the needle. In some embodiments, a duck-billed valveconfiguration may seal well when un-interrupted against pressure in onedirection.

In some embodiments of the injector 100, the reservoir 102 may bevisible through the wall of the housing 122. According to suchembodiments, if the administration of the medical fluid or drug productis interrupted as a consequence of the operation of the lock 118, thepatient or caregiver may be able to visually determine the amount of thefull dose remaining in the reservoir 102. In other embodiments, thereservoir 102 may be completely enclosed within the housing 122 withoutprovision for a window.

To address the situation wherein it may be difficult or impossible tovisualize the reservoir 102, a third group of embodiments of theinjector is illustrated in FIGS. 13-15. This group of embodiments may beused in conjunction with any of the embodiments of the injector 100described herein. These embodiments may be used with an injector with areservoir 102 including a bore 104 having a first end 106 and a secondend 108, and a plunger assembly 110 including a plunger 112 moveablewithin the bore 104 between the first and second ends 106, 108. Acannula 114 may also be included, having an operational state whereinthe cannula 114 is connected in fluid communication with the reservoir102. The injector 100 further includes a spring 116 coupled to theplunger assembly 110 to move the plunger 112 between the first andsecond ends 106, 108. All of these structures are illustrated in FIGS.1-3, for example, and are also applicable to the embodiment describedrelative to FIGS. 13-15.

In distinction to the previously described embodiments, the embodimentillustrated in FIGS. 13-15 includes an indicator 290 mechanicallycoupled to the plunger assembly 110. The reservoir 102, plunger arm 140,and indicator 290 are at least partially disposed within a housing 122.

A proximity sensor 120 is coupled to the indicator 290 and moveablerelative to the housing 122, the proximity sensor 120 having a firstsensor state wherein the proximity sensor 120 extends (e.g., extendsfully) from the housing 122 and a second sensor state wherein theproximity sensor 120 is retracted toward the housing 122 relative to thefirst sensor state. In this version, the sensor 120 resembles thepivoting sensor 120 of FIGS. 4-6 and 9-10, and as such, it should beappreciated that the indicator 290 could be implemented into theembodiments of FIGS. 4-6 and 9-10 or any other embodiments disclosedhereinabove. That is, the indicator 290 can be combined with otherinjectors with locks, as disclosed. In the version of FIGS. 14 and 15,the indicator 290 is coupled to the plunger assembly 110 with theproximity sensor 120 in the second sensor state and the indicator 290 isdecoupled from the plunger assembly 110 with the proximity sensor 120 inthe first sensor state.

The indicator 290 mirrors the internal motion of the plunger 112externally to the housing 122 to permit visualization. Once theproximity sensor 120 detects that the injector 100 has become detachedfrom the patient, the indicator 290 would be decoupled from the plunger112, such that the indicator 290 would reflect the portion of the doseremaining in the reservoir 102. According to certain embodiments, theindicator 290 may be reversibly coupled to the plunger assembly 110 sothat if the injector 100 permits the injection to resume after theinjector 100 is repositioned or otherwise adjusted, the indictor 290would continue to mirror the motion of the plunger assembly 110 when theinjection is resumed. According to other embodiments, the indicator 290may be irreversibly decoupled from the plunger assembly 110 so that thecondition of the injector 100 when an error in administration occurredwould be preserved. Preserving the condition of the injector 100 may beuseful in assisting the patient or caregiver in their determination forfuture action based on the amount administered through the intendedmethod of administration (i.e., prior to the occurrence) and thepatient's overall disease/therapy conditions.

For example, the plunger assembly 110 may include a plunger arm 140attached to the plunger 112, as illustrated in FIG. 14. According tosuch an embodiment, the indicator 290 may be mechanically coupled to theplunger arm 140 through a gear train 292 having at least one gear 294that is moveable into and out of engagement. The proximity sensor 120may be coupled to the at least one gear 294 to move the at least onegear 294 out of engagement and decouple the indicator 290 from theplunger arm 140 with the proximity sensor 120 in the first sensor state.

According to the embodiment illustrated in FIGS. 14 and 15, the geartrain 292 includes the moveable pinion gear 294, as well as two racks296, 298 formed on facing surfaces 300, 302 of the plunger arm 140 andthe indicator 290. When the gear 294 engages the racks 296, 298simultaneously, as shown in FIG. 15, the gear 294 transmits motion ofthe plunger arm 140 to the indicator 290. When the gear 294 isdisengaged from rack 296, as shown in FIG. 14, the indicator 290 isdecoupled from any motion of the plunger arm 140.

The pinion gear 294 is biased toward engagement with the racks 296, 298by a spring 304. A linkage 306 passes through the gear 294 at a firstend 308, and is attached to a further linkage 310 at a second end 312.The linkage 310 may be a flexible linkage (as illustrated), in the formof a string or cord. In other embodiments, the linkage 310 may include arigid mechanical linkage including additional levers, gears, couplings,etc. The depicted flexible linkage 310 may pass about a drum, wheel orpulley 314 and be connected to the proximity sensor 120. The proximitysensor 120 may be defined by a lever 316 having a first end 318 attachedto the housing 112 at a pivot 320 and a second 322 that is attached tothe linkage 310. The lever 316 may be biased to move clockwise about thepivot 320, as illustrated in FIGS. 14 and 15, by a further spring 324.

The injector 100 of any of the foregoing embodiments may be an on-bodyinjector, the injector 100 comprising a surface having adhesive appliedthereto to attach the injector 100 to a body of a patient. For example,FIGS. 16-18 illustrates an on-body injector 400 that may incorporate anyof the embodiments illustrated in FIGS. 1-15. In some embodiments, theinjector 400 may be a wearable, disposable system. The injector 400 mayinclude a disposable housing 402 that may be attached to a patient orwearer with adhesive, for example.

The disposable housing 402 may be made of a plastic material. As seen inFIG. 17, the housing 402 may be defined by two sections, a plate 404that is applied against the wearer's skin, and a dome 406 that isattached to the plate 404, preferably by a seal at an interface betweena peripheral edge 408 of the plate 404 and a peripheral edge 410 of thedome 406.

As shown in FIG. 17, the housing 402 has an interior surface 412defining an interior space 414, and an exterior surface 416. Inparticular, the plate 404 has an interior surface 418 and an exteriorsurface 420, and the dome 406 has an interior surface 422 and anexterior surface 424. According to the illustrated embodiment, theinterior surface 412 of the housing 402 is defined by the interiorsurfaces 418, 422 of the plate 404 and the dome 406, while the exteriorsurface 416 of the housing 402 is defined by the exterior surfaces 420,424 of the plate 404 and dome 406.

The housing 402 may be attached to the skin of the wearer. In someembodiments, an adhesive may be used. The adhesive may be adapted toreleasably secure the housing to skin during a single application. Asshown in FIG. 16, the adhesive is disposed in a layer 426 on a portion428 of the exterior surface 416 of the housing 402, and in particular onthe exterior surface 420 of the plate 404. The adhesive is covered witha removable, disposable sheet 430 prior to application of the housing402 to the skin of the wearer.

As seen in FIGS. 17 and 18, a reservoir 440, a drive 442, a cannula (orstructure, see below) 444, and an inserter 446 are disposed in thehousing 402. According to the illustrated embodiment, the reservoir 440may be defined at least in part by a combination of a rigid-walledcylinder or bore 450 having a port 452 at a first end 454 and a plunger456 fitted to move along a longitudinal axis 458 of the cylinder 450between a second end 460 and the first end 454 to force medical fluid ordrug product out of the reservoir 440 through the port 452 (FIG. 17).The movement of the plunger 456 may be caused by the operation of thedrive 442. Additionally, as shown, a valve 451 can be disposed at theexit of the port 452 between the reservoir 440 and a delivery line 453that is fluidly coupled to the cannula 444.

The drive 442 may include a plunger arm and a spring. The plunger armmay be in contact at least at a first end of the plunger 456 to urge theplunger 456 along the cylinder 450, and the spring may be coupled to theplunger arm to cause the plunger arm/plunger 456 to move along thelongitudinal axis 458. The combination of the plunger arm and spring mayalso be referred to as one example of a drive or an actuator. Othermechanisms, such as pressurized gases, materials undergoing phasechanges and the like, may be used as the drive 442 to apply a force tothe plunger 456 to move the plunger 456 along the cylinder 450. To thisextent, the drive 442 may be constructed according to the embodimentsdisclosed above relative to FIGS. 1-12, or any other embodiment capableof serving the intended purpose.

According to other embodiments, a non-rigid collapsible pouch may besubstituted for the rigid-walled cylinder 450 and the plunger 456illustrated in FIG. 17. In embodiments where the reservoir 450 is in theform of a non-rigid collapsible pouch, a spring-based mechanical systemmay be used to compress and pressurize the reservoir 450. In otherembodiments, a non-mechanical system may be used to move the plunger 456or compress the non-rigid collapsible reservoir. For example, agas-generating system may be used, including a two-component systemwherein the components are kept apart until the gas is to be generated,in which case they are combined. In some embodiments, a swellable gelmay be used, wherein the introduction of water from a source internal tothe device causes the gel to increase in dimension to move the plungeror compress the reservoir. As a further example, a propellant reservoirmay be opened and the propellant discharged to move the plunger 456 orcompress the reservoir. Embodiments of the present disclosure could beused to prevent motion of the structures used to move the plunger 456 orcompress the reservoir, thereby limiting such motion if the injector 400were to separate from the patient during delivery.

According to certain embodiments, the reservoir 440 may be a pre-filledcontainer, such as a pre-filled cartridge or a pre-filled syringe.Alternatively, the injector 400 may include a fill port 480 in fluidcommunication with the reservoir 440, the fill port 480 adapted toreceive a luer tip of a syringe, although a rubber septum may be usedinstead, for example. In use, a healthcare provider may inject themedical fluid or drug product from the syringe through the fill port 480into the reservoir 440, and the syringe may be provided as a pre-filledsyringe (filled with any of the materials mentioned above) to thehealthcare provider with the delivery injector 400 as a kit.

The cannula (or structure) 444 may have a retracted state wherein apointed end 490 (or, the entire cannula 444) may be withdrawn inside thehousing 402 and a deployed state wherein the pointed end 490 projectsfrom the housing 402, the inserter 446 moving the cannula (or structure)444 from the retracted state to the deployed state. In some embodiments,the injector 400 includes a proximity sensor 120 similar to any one ofthe proximity sensors 1210 described above and which may extend from thehousing 402 (specifically, the plate 404) in a similar fashion to thecannula 444, moving between extended and retracted states.

The cannula 444 may be hollow, and may be used to administer the medicalfluid or drug product directly to the patient. Alternatively, thestructure 444 may be used in conjunction with a cannula 492 fitted aboutthe structure 444, the structure 444 being used to insert the cannula492 into the patient through the injection site, and the medical fluidor drug product passing through the catheter 492 into the patient duringadministration. The injector 400 may, according to certain exemplaryembodiments, use a needle to automatically insert a soft cannula intothe subcutaneous tissue with the needle being withdrawn prior to passageof medical fluid or drug product through the soft cannula.

As illustrated in FIG. 17, the housing 402 (specifically the plate 404)may have an aperture or opening 494 to permit the cannula (or structure)444 (and optionally cannula 492) to pass therethrough. According tocertain embodiments, the aperture 494 may be unobstructed, such thatthere is no impediment or obstacle to the movement of the cannula 444(and catheter 492) through the opening 494. However, to better maintainthe sterility of the cannula 444 and the device's container closureintegrity (CCI), a septum may be disposed in or over the aperture 494.

The septum, which may be made of a rubber, may be disposed between thecannula 444 (and the space 414) and the patient's skin with the needle444 in the retracted state. In the deployed state, at least a portion ofthe needle 444 (i.e., the pointed end 490) will extend from the space414 through the septum. As such, the septum is always present as abarrier between the interior space 414 and the external environment.

In some embodiments, the injector 400 includes a controller 500. Thecontroller may include at least one processor and memory, the processorprogrammed to carry out the actions that the controller is adapted toperform, and the memory, including one or more tangible non-transitoryreadable memories, having executable instructions stored thereon, whichinstructions when executed by the at least one processor may cause theat least one processor to carry out the actions that the controller isadapted to perform. In other embodiments, the controller may includecircuitry that carries out the actions that the controller is adapted toperform. By way of example and not limitation, the controller 500 may beadapted to carry out any one of the methods described above relative tothe drug delivery system.

According to certain embodiments of the present disclosure, the lock andproximity sensor may be defined by a single structure, such as a plateor lever, or an assembly of structures, which collectively provide thefunction. Alternatively, the lock may be a structure defined separatelyfrom the proximity sensor. In such a case, the movement of the proximitysensor may be detected through the use of a switch, such as a mechanicalswitch or optical switch, which switch may be coupled to the controller500 and may provide information in the form of a signal (or signals, oran absence of signal (low vs. high)) to the controller 500 when theproximity sensor moves or changes positions or states. In someembodiments, the lock can be the valve 451 connected to the controller500, as depicted in FIGS. 17 and 18, and the proximity sensor caninclude an electrical sensor (e.g., a Hall effect sensor) or anelectromechanical sensor (e.g., a linear variable differentialtransformer (LVDT)), for example, mounted within the housing fordetecting the position of the movable cannula 444 or other movableproximity sensor mounted to the housing. The controller 500 may thus beoperatively coupled to the valve 451, and may be capable of transmittinginformation to the valve 451 in the form of a signal for changing thestate of the valve 451 between positions or states in response to thesignal received from the switch or other device coupled to the cannula444 or other proximity sensor. For example, the controller 500 may becoupled to an actuator, such as a linear actuator, that is capable ofmoving the valve 451 between opened and closed positions or states.

In some embodiments, other advantages of using the controller 500 caninclude defining the state of the lock or valve 451 as reversible orirreversible. For example, in some embodiments, the proximity sensor mayhave not only first and second states, but also one or more third states(e.g., intermediate states), where the lock (e.g., valve 451) maytransition from occupying a reversible condition to an irreversiblecondition. This functionality could be therefore achieved through theuse of the controller 500 in operable communication with the proximitysensor and lock (e.g., valve 451). In this manner, the sensitivity orthreshold for converting the lock condition from reversible toirreversible could be specifically managed by way of the logic orsoftware stored on a memory of the controller 500 based on the specificpatient, the specific medical fluid or drug product being administered,or generally any other parameter.

While the lock in FIGS. 17 and 18 has been described as a valve 451, inother embodiments, the lock can take other forms. For example, FIGS. 21and 22 depict an alternative version of the injector 400, wherein thelock includes a movable plate 461 similar to the proximity sensor 120described with respect to FIGS. 1-3, for example. The plate 461 isspring biased into the position illustrated in FIG. 21 such that similarto prior embodiments, upon application of the injector 400 to apatient's skin, the plate 461 retracts into the housing 402 and into theposition depicted in FIG. 22. As shown, the plate 461 also includes anaperture 465 through which the fluid line 453 of the injector 400passes. In FIGS. 21 and 22, the fluid line 453 is a flexible line. And,in FIG. 21, an interior edge 463 of the aperture 465 in the plate 461bears down against an upper sidewall of the fluid line 453 such that theplate 461 pinches the fluid line closed. In this manner, the interioredge 463 of the aperture 465 in the plate 461 limits or prevents fluidin the reservoir 440 from travelling past the pinched portion of thefluid line 453. The plate 461 thus serves as the lock. When the injector400 is applied to a patient's skin, the plate 461 retracts sufficientlyfar into the housing that the interior edge 463 of the aperture 465moves out of engagement with the fluid line, as shown in FIG. 22, suchthat medical fluid or drug product stored in the reservoir 440 canfreely pass through the fluid line 453 under the operation of the drive442.

The injector of any of the foregoing embodiments may be a hand-heldautoinjector 600, the injector comprising a needle shield that definesthe proximity sensor. See FIGS. 19 and 20. The autoinjector 600 mayinclude a housing 610 in which may be disposed assemblies or structuresthat insert or enable insertion of a cannula into the patient, and thatinject a medical fluid or drug product from the reservoir through thecannula into the patient. According to certain embodiments, the sameassemblies or structures that insert the cannula into the patient mayalso allow flow of the medical fluid or drug product from the reservoirthrough the cannula into the patient. The autoinjector 600 may alsoinclude assemblies or structures that connect the cannula to thereservoir, that withdraw the cannula into the housing 610, or thatdeploy other structures that will prevent contact with the cannula oncethe cannula has been removed from the patient. The specific embodimentof the autoinjector 600 discussed below is provided by way of exampleand not of limitation. In some embodiments, the autoinjector 600 may ormay not include assemblies or structures that direct or force insertionof the cannula (e.g., needle) into the patient. In some embodiments, thecannula may be substantially fixed relative to the housing of theautoinjector 600 such that insertion of the cannula into the patientsimply results from moving the cannula into contact with the patient.

In some embodiments, the drug delivery system 600 includes a reservoir612 and a cannula 614 having a first end 616 that may be connected orconnectable in fluid communication to the reservoir 612 and a second end618 that may be inserted into a patient. The cannula 614 may be, forexample, a rigid needle having a beveled edge that may be sized suchthat the second end 618 of the needle 614 is received under the skin soas to deliver a subcutaneous injection of the medical fluid or drugproduct within the reservoir 612. The first end 616 of the needle 614may be disposed through a wall 620 of the reservoir 612, and thus beconnected in fluid communication with the reservoir 612. As illustrated,the first end 616 of the needle 614 may be disposed only partiallythrough the wall 620 (which wall 620 may be a resealable septum orstopper, for example) such that the first end 616 of the needle 614 maynot be connected in fluid communication with the reservoir 612 until thesecond end 618 of the needle 614 is inserted into the patient. Soconfigured, the wall 620 of this embodiment is a lock, as used herein,and as will be described. Moreover, in some embodiments, once removedfrom the patient, the first end 616 of the needle 614 may again becomedisconnected from fluid communication with the reservoir 612. In such acircumstance, the first end 616 of the needle 614 may be described asconnectable in fluid communication with the reservoir 612, although itwill be recognized that there are other mechanisms by which the firstend 616 of the needle 614 may be connectable, but not connected, influid communication with the reservoir 612.

In some embodiments, the drug delivery device 600 includes a shield 622that may be deployed at least after the injection has been completed tolimit access to the second end 618 of the needle 614. According tocertain embodiments, the shield 622 may have a biasing element (such asa spring) that extends the shield 622 from the housing 610 such that adistal end 626 of the shield 622 extends beyond the second end 618 ofthe needle 614 except when the shield 622 is disposed against the skinand the injection of the needle 614 is actuated. In fact, the injectionof the needle 614 may be actuated according to certain embodiments ofthe autoinjector 600 by disposing the distal end 626 of the shield 622on or against the skin of the patient. According to certain embodimentsof the present disclosure, the shield 622 may define the proximitysensor 120.

In some embodiments, the drug delivery device 600 includes at least onedrive 630 that may be used to insert the second end 618 of the needle614 into the skin of the patient, and to inject the medical fluid ordrug product from the reservoir 612 through the needle 614 into thepatient. The drive 630 may include one or more springs, according tocertain embodiments. In other embodiments, the drive 630 may include asource of pressurized gas or a source of a material that undergoes aphase change, such that the escaping gas or phase changing material thatprovides a motive force that may be applied to the reservoir 612 toeject the medical fluid or drug product therefrom. According to stillother embodiments, the drive 630 may include an electromechanicalsystem, such as a motor.

The drive 630 may cooperate with a wall 632 of the reservoir 622 to movethat wall 632 toward the patient's skin. In accordance with such anembodiment, the wall 632 may be a stopper that is received within a bore634, and which may move along the bore 634 from a first end to a secondend to inject the medical fluid or drug product from the reservoir 612.The drive 630 may also cooperate with the wall 632 and/or the bore 634to move the reservoir 612 relative to the housing 610 so as to move thesecond end 618 of the needle 614 relative to the housing 610 and intothe patient. According to those embodiments wherein the drive 630cooperates with the stopper 632, this may occur before the first end 616of the needle 614 is in fluid communication with the reservoir 612.According to those embodiments wherein the drive cooperates with thebore 634, the drive may include one component (e.g., first spring) thatcooperates with the bore 634 to move the reservoir 612 and needle 614relative to the housing 610, and a second component (e.g., secondspring) that cooperates with the stopper 632 to move the stopper 632relative to the bore 634.

In some embodiments, the drive 630 is associated with an actuator 640.The actuator 640 activates the drive to cause the drive 630 to insertthe needle 614 and inject the medical fluid or drug product from thereservoir 612 through the needle 614 into the patient. The actuator 640may, according to certain embodiments, be the shield 622. According toother embodiments, the actuator 640 may be a button that may bedepressed by the user once the autoinjector 600 is disposed on oragainst the patient's skin. While the embodiment illustrated in FIGS. 19and 20 has the actuator 640 disposed at one end of the device, theactuator 640 could be disposed on the side of the device.

According to certain embodiments, the autoinjector 600 may include atleast one processor and memory. The controller may also include or becoupled to a power supply, e.g. a battery. The processor may beprogrammed to carry out the actions that the controller is adapted toperform and the memory may include one or more tangible non-transitoryreadable memories having executable instructions stored thereon, whichinstructions when executed by the at least one processor may cause theat least one processor to carry out the actions that the controller isadapted to perform. Alternatively, the controller may include othercircuitry that carries out the actions that the controller is adapted toperform.

Before the first end 616 penetrates the wall 620, the wall 620 seals thereservoir 612 from communicating with the needle 614 and thereby limitsthe movement of the wall 632 or stopper in the bore 634. In this way,the wall 620 is a lock, as used herein. But as mentioned above, as thesecond end 618 of the needle 614 of the autoinjector 600 of FIGS. 19 and20 is inserted into a patient, the first end 616 of the needle 614penetrates the wall 620 to become in fluid communication with thereservoir 612. In some embodiments, once the second end 618 of theneedle 614 is removed from the patient, the first end 616 of the needle614 may again become disconnected from fluid communication with thereservoir 612 by, for example, being drawn back through the wall 620 atleast such that the first end 616 of the needle 614 no longer resideswithin the reservoir 612, but rather resides inside of the wall 620 or,said another away, resides at a point between opposing surfaces of thewall 620. In this way, the wall 620 can automatically seal the openingthrough which the first end 616 of the needle 614 previously passed intothe reservoir, and thereby locks the fluid delivery mechanism.

FIGS. 23 and 24 illustrate an alternative version of the autoinjector600 depicted in FIGS. 19 and 20 for facilitating this functionality. InFIGS. 23 and 24, the autoinjector 600 includes a needle assembly 700 fordisconnecting the needle 614 from fluid communication with the reservoir612 when the needle 614 is removed from the patient. As illustrated, theneedle assembly 700 includes a retainer 702 and a biasing member such asspring 704. The retainer 702 is fixed to the needle 614 and slidablydisposed in the housing 610 adjacent to the shield 622. The spring 704can be a coil spring and is disposed between the wall 620 of thereservoir 612 and the retainer 702. In the depicted version, a topsurface 706 of the retainer 702 defines an annular recess 708 into whicha first end 710 of the spring 704 is seated. A second end 712 of thespring 704 is seated against the wall 620 (or a component surroundingthe wall 620). So configured, the spring 704 biases the needle assembly700 away from the reservoir 612 and the wall 620 (i.e., downwardrelative to the orientation of the autoinjector 600 depicted in FIG.23).

Accordingly, when the second end 618 of the needle 614 is inserted intoa patient, a bottom surface 714 of the retainer 702 bears against thepatient's skin and therefore serves as the proximity sensor in thisembodiment. As a force is applied to the autoinjector 600 in thedirection of the patient's skin, the needle assembly 700 moves into thehousing 610 against the force of the spring 704 such that the first end616 of the needle 614 fully penetrates the wall 620 and becomes in fluidcommunication with the reservoir 612. This allows medicament in thereservoir 612 to pass into the first end 616 of the needle 614 forpatient administration. When the needle 614 is removed from the patient,the spring 702 naturally biases the retainer 702 back into the positiondepicted in FIG. 23 which in turn draws the needle 614 with it becausethe needle 614 and retainer 702 are fixed together. In the version shownin FIG. 23, the housing 610 of the autoinjector 600 further includes oneor more stops 716 carried by the inside of the housing 610 adjacent tothe shield 622. As the spring 702 biases the retainer 702 away from thereservoir 612, the retainer 702 comes into contact with the stop(s) 716.The stop(s) 716 therefore limit the displacement of the retainer 702 andneedle 614 away from the reservoir 612 such that when the retainer 702engages the stop(s) 716, the first end 616 of the needle 614 is fullywithdrawn from and out of fluid communication with the reservoir 612. Inthe depicted version, this also means that the first end 616 of theneedle 614 resides within the wall 620, which serves as the lock. Thatis, the wall 620 in this configuration limits further movement of thewall 623 or stopper by sealing the flow path through the needle 614 whenthe device is removed from the patient. In this version, the wall 620,as the lock, is reversible because when the second end 618 of the needle614 is subsequently re-inserted into a patient, for example, the needleassembly 700 can again move into the housing 610 against the force ofthe spring 704 such that the first end 616 of the needle 614 fullypenetrates the wall 620 and becomes in fluid communication with thereservoir 612. In other versions, the device may include additionalstructures that prevent such reversible action from occurring.

The present disclosure describes various systems and methods for usewith a drug delivery device. The system, methods or drug delivery devicecan comprise use of a medical fluid or drug product listed below, withthe caveat that the following list should neither be considered to beall inclusive nor limiting. The medical fluid or drug product will becontained in a reservoir. In some instances, the reservoir is a primarycontainer that is either filled or pre-filled for treatment with themedical fluid or drug product. The primary container can be a cartridgeor a pre-filled syringe.

For example, the drug delivery device or more specifically the reservoirof the device may be filled with colony stimulating factors, such asgranulocyte colony-stimulating factor (G-CSF). Such G-CSF agentsinclude, but are not limited to, Neupogen® (filgrastim) and Neulasta®(pegfilgrastim). In various other embodiments, the drug delivery devicemay be used with various pharmaceutical products, such as anerythropoiesis stimulating agent (ESA), which may be in a liquid or alyophilized form. An ESA is any molecule that stimulates erythropoiesis,such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo®(epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta),Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon®(epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa),epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta),Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa,epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well asthe molecules or variants or analogs thereof as disclosed in thefollowing patents or patent applications, each of which is hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689;and PCT Publ. Nos. WO 91/05867; WO 95/05465; WO 96/40772; WO 00/24893;WO 01/81405; and WO 2007/136752.

An ESA can be an erythropoiesis stimulating protein. As used herein,“erythropoiesis stimulating protein” means any protein that directly orindirectly causes activation of the erythropoietin receptor, forexample, by binding to and causing dimerization of the receptor.Erythropoiesis stimulating proteins include erythropoietin and variants,analogs, or derivatives thereof that bind to and activate erythropoietinreceptor; antibodies that bind to erythropoietin receptor and activatethe receptor; or peptides that bind to and activate erythropoietinreceptor. Erythropoiesis stimulating proteins include, but are notlimited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega,epoetin iota, epoetin zeta, and analogs thereof, pegylatederythropoietin, carbamylated erythropoietin, mimetic peptides (includingEMP1/hematide), and mimetic antibodies. Exemplary erythropoiesisstimulating proteins include erythropoietin, darbepoetin, erythropoietinagonist variants, and peptides or antibodies that bind and activateerythropoietin receptor (and include compounds reported in U.S. Publ.Nos. 2003/0215444 and 2006/0040858, the disclosures of each of which isincorporated herein by reference in its entirety) as well aserythropoietin molecules or variants or analogs thereof as disclosed inthe following patents or patent applications, which are each hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086;6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369;7,030,226; 7,084,245; and 7,217,689; US Publ. Nos. 2002/0155998;2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694;2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834;2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564;2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879; 2005/0158822;2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211;2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906; and2006/0111279; and PCT Publ. Nos. WO 91/05867; WO 95/05465; WO 99/66054;WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO 02/014356; WO02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO 03/029291; WO2003/055526; WO 2003/084477; WO 2003/094858; WO 2004/002417; WO2004/002424; WO 2004/009627; WO 2004/024761; WO 2004/033651; WO2004/035603; WO 2004/043382; WO 2004/101600; WO 2004/101606; WO2004/101611; WO 2004/106373; WO 2004/018667; WO 2005/001025; WO2005/001136; WO 2005/021579; WO 2005/025606; WO 2005/032460; WO2005/051327; WO 2005/063808; WO 2005/063809; WO 2005/070451; WO2005/081687; WO 2005/084711; WO 2005/103076; WO 2005/100403; WO2005/092369; WO 2006/50959; WO 2006/02646; and WO 2006/29094.

Examples of other pharmaceutical products for use with the device mayinclude, but are not limited to, antibodies such as Vectibix®(panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); otherbiological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF,hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such asSensipar® (cinacalcet). The device may also be used with a therapeuticantibody, a polypeptide, a protein or other chemical, such as an iron,for example, ferumoxytol, iron dextrans, ferric glyconate, and ironsucrose. The pharmaceutical product may be in liquid form, orreconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and thelike (also referred to as RANKL specific antibodies, peptibodies and thelike), including fully humanized and human OPGL specific antibodies,particularly fully humanized monoclonal antibodies, including but notlimited to the antibodies described in PCT Publ. No. WO 03/002713, whichis incorporated herein in its entirety as to OPGL specific antibodiesand antibody related proteins, particularly those having the sequencesset forth therein, particularly, but not limited to, those denotedtherein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including the OPGLspecific antibodies having either the light chain of SEQ ID NO: 2 as setforth therein in FIG. 2 and/or the heavy chain of SEQ ID NO:4, as setforth therein in FIG. 4, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing Publication;

Myostatin binding proteins, peptibodies, and related proteins, and thelike, including myostatin specific peptibodies, particularly thosedescribed in US Publ. No. 2004/0181033 and PCT Publ. No. WO 2004/058988,which are incorporated by reference herein in their entiretyparticularly in parts pertinent to myostatin specific peptibodies,including but not limited to peptibodies of the mTN8-19 family,including those of SEQ ID NOS: 305-351, including TN8-19-1 throughTN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies of the mL2 family ofSEQ ID NOS: 357-383; the mL15 family of SEQ ID NOS: 384-409; the mL17family of SEQ ID NOS: 410-438; the mL20 family of SEQ ID NOS: 439-446;the mL21 family of SEQ ID NOS: 447-452; the mL24 family of SEQ ID NOS:453-454; and those of SEQ ID NOS: 615-631, each of which is individuallyand specifically incorporated by reference herein in their entiretyfully as disclosed in the foregoing publication;

IL-4 receptor specific antibodies, peptibodies, and related proteins,and the like, particularly those that inhibit activities mediated bybinding of IL-4 and/or IL-13 to the receptor, including those describedin PCT Publ. No. WO 2005/047331 or PCT Appl. No. PCT/US2004/37242 and inUS Publ. No. 2005/112694, which are incorporated herein by reference intheir entirety particularly in parts pertinent to IL-4 receptor specificantibodies, particularly such antibodies as are described therein,particularly, and without limitation, those designated therein: L1H1;L1H2; L1H3; L1H4; L1H5; L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1;L2H2; L2H3; L2H4; L2H5; L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12;L2H13; L2H14; L3H1; L4H1; L5H1; L6H1, each of which is individually andspecifically incorporated by reference herein in its entirety fully asdisclosed in the foregoing publication;

Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies,and related proteins, and the like, including but not limited to thosedescribed in U.S. Publ. No. 2004/097712A1, which is incorporated hereinby reference in its entirety in parts pertinent to IL1-R1 specificbinding proteins, monoclonal antibodies in particular, especially,without limitation, those designated therein: 15CA, 26F5, 27F2, 24E12,and 10H7, each of which is individually and specifically incorporated byreference herein in its entirety fully as disclosed in theaforementioned U.S. publication;

Ang2 specific antibodies, peptibodies, and related proteins, and thelike, including but not limited to those described in PCT Publ. No. WO03/057134 and U.S. Publ No. 2003/0229023, each of which is incorporatedherein by reference in its entirety particularly in parts pertinent toAng2 specific antibodies and peptibodies and the like, especially thoseof sequences described therein and including but not limited to: L1(N);L1(N) WT; L1(N) 1K WT; 2×L1(N); 2×L1(N) WT; Con4 (N), Con4 (N) 1K WT,2×Con4 (N) 1K; L1C; L1C 1K; 2×L1C; Con4C; Con4C 1K; 2×Con4C 1K; Con4-L1(N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N); TN8-14 (N); Con 1 (N),also including anti-Ang 2 antibodies and formulations such as thosedescribed in PCT Publ. No. WO 2003/030833 which is incorporated hereinby reference in its entirety as to the same, particularly Ab526; Ab528;Ab531; Ab533; Ab535; Ab536; Ab537; Ab540; Ab543; Ab544; Ab545; Ab546;A551; Ab553; Ab555; Ab558; Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK;AbG1D4; AbGC1E8; AbH1C12; Ab1A1; Ab1F; Ab1K, Ab1P; and Ab1P, in theirvarious permutations as described therein, each of which is individuallyand specifically incorporated by reference herein in its entirety fullyas disclosed in the foregoing publication;

NGF specific antibodies, peptibodies, and related proteins, and the likeincluding, in particular, but not limited to those described in US Publ.No. 2005/0074821 and U.S. Pat. No. 6,919,426, which are incorporatedherein by reference in their entirety particularly as to NGF-specificantibodies and related proteins in this regard, including in particular,but not limited to, the NGF-specific antibodies therein designated 4D4,4G6, 6H9, 7H2, 14D10 and 14D11, each of which is individually andspecifically incorporated by reference herein in its entirety fully asdisclosed in the foregoing publication;

CD22 specific antibodies, peptibodies, and related proteins, and thelike, such as those described in U.S. Pat. No. 5,789,554, which isincorporated herein by reference in its entirety as to CD22 specificantibodies and related proteins, particularly human CD22 specificantibodies, such as but not limited to humanized and fully humanantibodies, including but not limited to humanized and fully humanmonoclonal antibodies, particularly including but not limited to humanCD22 specific IgG antibodies, such as, for instance, a dimer of ahuman-mouse monoclonal hLL2 gamma-chain disulfide linked to ahuman-mouse monoclonal hLL2 kappa-chain, including, but limited to, forexample, the human CD22 specific fully humanized antibody inEpratuzumab, CAS registry number 501423-23-0;

IGF-1 receptor specific antibodies, peptibodies, and related proteins,and the like, such as those described in PCT Publ. No. WO 06/069202,which is incorporated herein by reference in its entirety as to IGF-1receptor specific antibodies and related proteins, including but notlimited to the IGF-1 specific antibodies therein designated L1H1, L2H2,L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11, L12H12,L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20, L21H21,L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29, L30H30,L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38, L39H39,L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47, L48H48,L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments andderivatives thereof, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing International Publication;

Also among non-limiting examples of anti-IGF-1R antibodies for use inthe methods and compositions of the present disclosure are each and allof those described in:

(i) US Publ. No. 2006/0040358 (published Feb. 23, 2006), 2005/0008642(published Jan. 13, 2005), 2004/0228859 (published Nov. 18, 2004),including but not limited to, for instance, antibody 1A (DSMZ DepositNo. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589), antibody23 (DSMZ Deposit No. DSM ACC 2588) and antibody 18 as described therein;

(ii) PCT Publ. No. WO 06/138729 (published Dec. 28, 2006) and WO05/016970 (published Feb. 24, 2005), and Lu et al., 2004, J Biol. Chem.279:2856-65, including but not limited to antibodies 2F8, A12, andIMC-A12 as described therein;

(iii) PCT Publ. No. WO 07/012614 (published Feb. 1, 2007), WO 07/000328(published Jan. 4, 2007), WO 06/013472 (published Feb. 9, 2006), WO05/058967 (published Jun. 30, 2005), and WO 03/059951 (published Jul.24, 2003); (iv) US Publ. No. 2005/0084906 (published Apr. 21, 2005),including but not limited to antibody 7C10, chimaeric antibody C7C10,antibody h7C10, antibody 7H2M, chimaeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version2, humanized antibody 7C10 version 3, and antibody 7H2HM, as describedtherein;

(v) US Publ. Nos. 2005/0249728 (published Nov. 10, 2005), 2005/0186203(published Aug. 25, 2005), 2004/0265307 (published Dec. 30, 2004), and2003/0235582 (published Dec. 25, 2003) and Maloney et al., 2003, CancerRes. 63:5073-83, including but not limited to antibody EM164, resurfacedEM164, humanized EM164, huEM164 v1.0, huEM164 v1.1, huEM164 v1.2, andhuEM164 v1.3 as described therein;

(vi) U.S. Pat. No. 7,037,498 (issued May 2, 2006), US Publ. Nos.2005/0244408 (published Nov. 30, 2005) and 2004/0086503 (published May6, 2004), and Cohen, et al., 2005, Clinical Cancer Res. 11:2063-73,e.g., antibody CP-751,871, including but not limited to each of theantibodies produced by the hybridomas having the ATCC accession numbersPTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, andantibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, asdescribed therein;

(vii) US Publ. Nos. 2005/0136063 (published Jun. 23, 2005) and2004/0018191 (published Jan. 29, 2004), including but not limited toantibody 19D12 and an antibody comprising a heavy chain encoded by apolynucleotide in plasmid 15H12/19D12 HCA (γ4), deposited at the ATCCunder number PTA-5214, and a light chain encoded by a polynucleotide inplasmid 15H12/19D12 LCF (κ), deposited at the ATCC under numberPTA-5220, as described therein; and

(viii) US Publ. No. 2004/0202655 (published Oct. 14, 2004), includingbut not limited to antibodies PINT-6A1, PINT-7A2, PINT-7A4, PINT-7A5,PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3,PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2,PINT-12A3, PINT-12A4, and PINT-12A5, as described therein; each and allof which are herein incorporated by reference in their entireties,particularly as to the aforementioned antibodies, peptibodies, andrelated proteins and the like that target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteinsand the like (“B7RP-1,” also is referred to in the literature as B7H2,ICOSL, B7h, and CD275), particularly B7RP-specific fully humanmonoclonal IgG2 antibodies, particularly fully human IgG2 monoclonalantibody that binds an epitope in the first immunoglobulin-like domainof B7RP-1, especially those that inhibit the interaction of B7RP-1 withits natural receptor, ICOS, on activated T cells in particular,especially, in all of the foregoing regards, those disclosed in U.S.Publ. No. 2008/0166352 and PCT Publ. No. WO 07/011941, which areincorporated herein by reference in their entireties as to suchantibodies and related proteins, including but not limited to antibodiesdesignated therein as follow: 16H (having light chain variable and heavychain variable sequences SEQ ID NO:1 and SEQ ID NO:7 respectivelytherein); 5D (having light chain variable and heavy chain variablesequences SEQ ID NO:2 and SEQ ID NO:9 respectively therein); 2H (havinglight chain variable and heavy chain variable sequences SEQ ID NO:3 andSEQ ID NO:10 respectively therein); 43H (having light chain variable andheavy chain variable sequences SEQ ID NO:6 and SEQ ID NO:14 respectivelytherein); 41H (having light chain variable and heavy chain variablesequences SEQ ID NO:5 and SEQ ID NO:13 respectively therein); and 15H(having light chain variable and heavy chain variable sequences SEQ IDNO:4 and SEQ ID NO:12 respectively therein), each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing U.S. Publication;

IL-15 specific antibodies, peptibodies, and related proteins, and thelike, such as, in particular, humanized monoclonal antibodies,particularly antibodies such as those disclosed in U.S. Publ. Nos.2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No.7,153,507, each of which is incorporated herein by reference in itsentirety as to IL-15 specific antibodies and related proteins, includingpeptibodies, including particularly, for instance, but not limited to,HuMax IL-15 antibodies and related proteins, such as, for instance,146B7;

IFN gamma specific antibodies, peptibodies, and related proteins and thelike, especially human IFN gamma specific antibodies, particularly fullyhuman anti-IFN gamma antibodies, such as, for instance, those describedin US Publ. No. 2005/0004353, which is incorporated herein by referencein its entirety as to IFN gamma specific antibodies, particularly, forexample, the antibodies therein designated 1118; 1118*; 1119; 1121; and1121*. The entire sequences of the heavy and light chains of each ofthese antibodies, as well as the sequences of their heavy and lightchain variable regions and complementarity determining regions, are eachindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing US Publication and inThakur et al., Mol. Immunol. 36:1107-1115 (1999). In addition,description of the properties of these antibodies provided in theforegoing US publication is also incorporated by reference herein in itsentirety. Specific antibodies include those having the heavy chain ofSEQ ID NO: 17 and the light chain of SEQ ID NO:18; those having theheavy chain variable region of SEQ ID NO:6 and the light chain variableregion of SEQ ID NO:8; those having the heavy chain of SEQ ID NO:19 andthe light chain of SEQ ID NO:20; those having the heavy chain variableregion of SEQ ID NO:10 and the light chain variable region of SEQ IDNO:12; those having the heavy chain of SEQ ID NO:32 and the light chainof SEQ ID NO:20; those having the heavy chain variable region of SEQ IDNO:30 and the light chain variable region of SEQ ID NO:12; those havingthe heavy chain sequence of SEQ ID NO:21 and the light chain sequence ofSEQ ID NO:22; those having the heavy chain variable region of SEQ IDNO:14 and the light chain variable region of SEQ ID NO:16; those havingthe heavy chain of SEQ ID NO:21 and the light chain of SEQ ID NO:33; andthose having the heavy chain variable region of SEQ ID NO:14 and thelight chain variable region of SEQ ID NO:31, as disclosed in theforegoing US Publication. A specific antibody contemplated is antibody1119 as disclosed in foregoing US Publication and having a completeheavy chain of SEQ ID NO:17 as disclosed therein and having a completelight chain of SEQ ID NO:18 as disclosed therein;

TALL-1 specific antibodies, peptibodies, and the related proteins, andthe like, and other TALL specific binding proteins, such as thosedescribed in U.S. Publ. Nos. 2003/0195156 and 2006/0135431, each ofwhich is incorporated herein by reference in its entirety as to TALL-1binding proteins, particularly the molecules of Tables 4 and 5B, each ofwhich is individually and specifically incorporated by reference hereinin its entirety fully as disclosed in the foregoing US Publications;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,756,480, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,835,809, which is herein incorporated by reference in its entirety,particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, andrelated proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF)described in US Publ. No. 2005/0118643 and PCT Publ. No. WO 2005/017107,huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5 described in U.S.Pat. Nos. 5,686,292 and 6,468,529 and in PCT Publ. No. WO 96/38557, eachof which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike, such as those described in U.S. Pat. No. 7,521,048, which isherein incorporated by reference in its entirety, particularly in partspertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in US Publ. No.2009/0234106, which is herein incorporated by reference in its entirety,particularly in parts pertinent to proteins that bind Activin A;

TGF-beta specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. Pat. No.6,803,453 and US Publ. No. 2007/0110747, each of which is hereinincorporated by reference in its entirety, particularly in partspertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins,and the like, including but not limited to those described in PCT Publ.No. WO 2006/081171, which is herein incorporated by reference in itsentirety, particularly in parts pertinent to proteins that bindamyloid-beta proteins. One antibody contemplated is an antibody having aheavy chain variable region comprising SEQ ID NO: 8 and a light chainvariable region having SEQ ID NO: 6 as disclosed in the InternationalPublication;

c-Kit specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in Publ. No. 2007/0253951,which is incorporated herein by reference in its entirety, particularlyin parts pertinent to proteins that bind c-Kit and/or other stem cellfactor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. application Ser.No. 11/086,289, which is incorporated herein by reference in itsentirety, particularly in parts pertinent to proteins that bind OX40Land/or other ligands of the OX40 receptor; and

Other exemplary proteins, including Activase® (alteplase, tPA); Aranesp®(darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab);insulin in solution; Infergen® (interferon alfacon-1); Natrecor®(nesiritide; recombinant human B-type natriuretic peptide (hBNP);Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide®(epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab,anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™(eculizumab); pexelizumab (anti-C5 complement); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio®(lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4);Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumabmertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega®(oprelvekin, human interleukin-11); Neulasta® (pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF,hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonalantibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFαmonoclonal antibody); Reopro® (abciximab, anti-GP lIb/Ilia receptormonoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin®(bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2α); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab);Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portionof human IgG1 and the extracellular domains of both IL-1 receptorcomponents (the Type I receptor and receptor accessory protein)); VEGFtrap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan);Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonalantibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFcfusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFαmAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb);HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab);M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab,anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficileToxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC);anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MYO-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513;anti-Mannose Receptor/hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRαantibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 humanmAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; anti-ZP3 mAb(HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.

Also included can be a sclerostin antibody, such as but not limited toromosozumab, blosozumab, or BPS 804 (Novartis). Further included can betherapeutics such as rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant,panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally,included in the device can be a monoclonal antibody (IgG) that bindshuman Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), e.g. U.S.Pat. No. 8,030,547, U.S. Ser. No. 13/469,032, WO2008/057457,WO2008/057458, WO2008/057459, WO2008/063382, WO2008/133647,WO2009/100297, WO2009/100318, WO2011/037791, WO2011/053759,WO2011/053783, WO2008/125623, WO2011/072263, WO2009/055783,WO2012/0544438, WO2010/029513, WO2011/111007, WO2010/077854,WO2012/088313, WO2012/101251, WO2012/101252, WO2012/101253,WO2012/109530, and WO2001/031007.

Also included can be talimogene laherparepvec or another oncolytic HSVfor the treatment of melanoma or other cancers. Examples of oncolyticHSV include, but are not limited to talimogene laherparepvec (U.S. Pat.Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (U.S. Pat. No. 7,981,669);OrienX010 (Lei et al., 2013, World Journal of Gastroenterology,19:5138-5143); G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargeheset al. 2002, Cancer Gene Ther, 2002, 9 (12): 967-978).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors ofmetalloproteinases (TIMPs) and are important in many natural process.TIMP-3 is expressed by various cells or and is present in theextracellular matrix; it inhibits all the major cartilage-degradingmetalloproteases, and may play a role in role in many degradativediseases of connective tissue, including rheumatoid arthritis andosteoarthritis, as well as in cancer and cardiovascular conditions. Theamino acid sequence of TIMP-3, and the nucleic acid sequence of a DNAthat encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issuedMay 13, 2003, the disclosure of which is incorporated by referenceherein. Description of TIMP mutations can be found in U.S. 61/782,613,U.S. 61/798,160, U.S. 61/802,988, and U.S. 61/940,67.

Also included are antagonistic antibodies for human calcitoningene-related peptide (CGRP) receptor and bispecific antibody moleculethat target the CGRP receptor and other headache targets. Furtherinformation concerning these molecule can be found in WO2A075238A1.

Additionally, a bispecific T cell engager antibody (BiTe), e.g.Blinotumomab can be used in the device. Alternatively, included can bean APJ large molecule agonist e.g., apelin or analogues thereof in thedevice. Information relating to such molecules can be found inPCT/2013/075773.

Although the preceding text sets forth a detailed description ofdifferent embodiments of the disclosure, it should be understood thatthe legal scope of the invention is defined by the words of the claimsset forth at the end of this patent. The detailed description is to beconstrued as exemplary only and does not describe every possibleembodiment of the invention because describing every possible embodimentwould be impractical, if not impossible. Numerous alternativeembodiments could be implemented, using either current technology ortechnology developed after the filing date of this patent, that wouldstill fall within the scope of the claims defining the invention.

It should also be understood that, unless a term is expressly defined inthis patent using the sentence “As used herein, the term ‘_(——————)’ ishereby defined to mean . . . ” or a similar sentence, there is no intentto limit the meaning of that term, either expressly or by implication,beyond its plain or ordinary meaning, and such term should not beinterpreted to be limited in scope based on any statement made in anysection of this patent (other than the language of the claims). To theextent that any term recited in the claims at the end of this patent isreferred to in this patent in a manner consistent with a single meaning,that is done for sake of clarity only so as to not confuse the reader,and it is not intended that such claim term be limited, by implicationor otherwise, to that single meaning. Finally, unless a claim element isdefined by reciting the word “means” and a function without the recitalof any structure, it is not intended that the scope of any claim elementbe interpreted based on the application of 35 U.S.C. § 112, sixthparagraph.

What is claimed:
 1. An on-body injector comprising: a reservoirincluding a bore having a first end and a second end, and a plungerassembly including a plunger moveable within the bore between the firstand second ends; a cannula having an operational state wherein thecannula is connected in fluid communication with the reservoir; a drivecoupled to the plunger assembly to move the plunger between the firstand second ends for moving a drug product out of the reservoir andthrough the cannula; a housing, wherein the reservoir, the cannula, andthe drive are disposed at least partially within the housing; aproximity sensor operably coupled to move relative to the housing, theproximity sensor having a first sensor state wherein the proximitysensor extends from the housing and a second sensor state wherein theproximity sensor is retracted toward the housing relative to the firstsensor state; a biasing member configured to bias the proximity sensortoward the first sensor state; and a lock operably coupled to theproximity sensor, the lock having a first position resisting movement ofthe plunger between the first and second ends of the reservoir when theproximity sensor is in the first sensor state and the lock having asecond position permitting movement of the plunger between the first andsecond ends of the reservoir when the proximity sensor is in the secondsensor state.
 2. The on-body injector of claim 1, wherein the lockcomprises a wall of a plate that moves along a line of motion and isoperably coupled to one of the plunger assembly and the drive when theproximity sensor is in the first sensor state.
 3. The on-body injectorof claim 2, wherein the plate has a first end that defines the wall ofthe lock and a second end that defines the proximity sensor.
 4. Theon-body injector of claim 2, wherein: the plunger assembly includes aplunger arm attached to the plunger; the wall of the lock abuts theplunger arm to limit movement of the plunger when the lock is coupled tothe plunger assembly; and the proximity sensor is coupled to the wall,where the wall abuts the plunger arm when the proximity sensor is in thefirst sensor state and the is spaced from the plunger arm when theproximity sensor is in the second sensor state.
 5. The on-body injectorof claim 4, wherein: the plunger arm has at least one shoulder formedthereon; and the wall of the lock abuts the at least one shoulder of theplunger arm to limit movement of the plunger when the lock is coupled tothe plunger assembly.
 6. The on-body injector of claim 1, wherein thelock comprises a wall of a lever that moves about a pivot and isoperably coupled to one of the plunger assembly and the drive when theproximity sensor is in the first sensor state.
 7. The on-body injectorof claim 6, wherein the lever has a first end disposable within thehousing and defining the wall of the lock, and a second end disposableoutside of the housing and defining the proximity sensor.
 8. The on-bodyinjector of claim 1, wherein the drive comprises a spring.
 9. Theon-body injector of claim 8, wherein the lock is selectively coupled toone of the plunger and the spring when the proximity sensor is in thefirst sensor state.
 10. The on-body injector of claim 9, wherein a wallof the lock abuts the spring to limit movement of the plunger when thelock is coupled to the plunger assembly; and the proximity sensor isattached to the wall, where the wall abuts the spring when the proximitysensor is in the first sensor state and the wall is spaced from thespring when the proximity sensor is in the second sensor state.
 11. Theon-body injector of claim 1, wherein the drive comprises a gas sourceand the lock comprises a vent operably coupled to the gas source toexhaust positive pressure from the gas source when the proximity sensoris in the first sensor state.
 12. The on-body injector of claim 11,further comprising a chamber disposed between and connecting the gassource and the reservoir, the vent disposed in a wall of the chamber.13. The on-body injector of claim 11, wherein the vent comprises a sealand a vent cannula, wherein the vent cannula pierces the seal when theproximity sensor is in the first sensor state.
 14. The on-body injectorof claim 13, further comprising a vent lever having a first endconnected to the vent cannula and a second end connected to theproximity sensor such that movement of the proximity sensor istransmitted to the vent cannula via the vent lever.
 15. The on-bodyinjector of claim 1, wherein the lock comprises a valve disposed betweenthe reservoir and the cannula, the valve being movable between open andclosed states and occupying the closed state when the proximity sensoris in the first sensor state.
 16. The on-body injector of claim 15,further comprising a controller coupled to the proximity sensor and thevalve for positioning the valve in the closed state when the proximitysensor is in the first sensor state.
 17. The on-body injector of claim15, further comprising a fluid line disposed between and connecting thereservoir and the cannula, the valve disposed on the fluid line.
 18. Theon-body injector of claim 1, further comprising a flexible fluid linedisposed between the reservoir and the cannula.
 19. The on-body injectorof claim 18, comprising a movable plate, wherein the movable platecomprises an aperture through which the flexible fluid line is disposed.20. The on-body injector of claim 1, wherein the lock comprises a walland a first end of the cannula resides within the wall and out of fluidcommunication with the reservoir when the proximity sensor is in thefirst sensor state.
 21. The on-body injector of claim 20, furthercomprising a biasing member biasing the first end of the cannula toreside within the wall.
 22. The on-body injector of claim 20, whereinthe first end of the cannula penetrates the wall and is in fluidcommunication with the reservoir when the proximity sensor is in thesecond sensor state.
 23. The on-body injector of claim 1, furthercomprising an indicator selectively coupled to the plunger assembly whenthe proximity sensor is in the second sensor state and selectivelyde-coupled from the plunger assembly when the proximity sensor is in thefirst sensor state.
 24. The on-body injector of claim 23, wherein theindicator is mechanically coupled to the plunger assembly when theproximity sensor is in the second sensor state.
 25. The on-body injectorof claim 24, wherein the plunger assembly comprises a plunger armattached to the plunger, the indicator being selectively mechanicallycoupled to the plunger arm through a gear train having at least one gearthat is moveable into and out of engagement with the plunger arm, andthe proximity sensor is coupled to the at least one gear to move the atleast one gear out of engagement with the plunger arm and decouple theindicator from the plunger arm with the proximity sensor in the firstsensor state.
 26. The on-body injector of claim 1, comprising anindicator disposed at an exterior surface of the housing, the indicatorbeing operable to track movement of the plunger within the bore of thereservoir when the proximity sensor is in the second sensor state andnot being operable to track movement of the plunger within the bore ofthe reservoir when the proximity sensor is in the first sensor state.27. The on-body injector of claim 26, wherein moving the proximitysensor from the second sensor state to the first sensor state decouplesthe indicator from the plunger such that the indicator does not trackmovement of the plunger within the bore of the reservoir.
 28. Theon-body injector of claim 1, the proximity sensor comprising a leverhaving a first end and a second end, the first end of the lever beingpivotably attached within the housing, the second end of the leverextending outside of the housing in the first sensor state.
 29. Theon-body injector of claim 28, the first end of the lever being pivotallyattached at a pivot within the housing, the biasing member beingconfigured to exert a biasing force on the first end of the lever at adistance away from the pivot.
 30. The on-body injector of claim 29, thebiasing member comprising a spring.
 31. The on-body injector of claim30, the spring being linearly compressible.
 32. The on-body injector ofclaim 1, wherein the lock mechanically resists movement of the plungerbetween the first and second ends of the reservoir when the proximitysensor is in the first sensor state.
 33. An on-body injector comprising:a reservoir including a bore having a first end and a second end, and aplunger assembly including a plunger moveable within the bore betweenthe first and second ends; a cannula having an operational state whereinthe cannula is connected in fluid communication with the reservoir; adrive coupled to the plunger assembly to move the plunger between thefirst and second ends for moving a drug product out of the reservoir andthrough the cannula; a housing, wherein the reservoir, the cannula, andthe drive are disposed at least partially within the housing; aproximity sensor operably coupled to move relative to the housing, theproximity sensor having a first sensor state wherein the proximitysensor extends from the housing and a second sensor state wherein theproximity sensor is retracted toward the housing relative to the firstsensor state; and an indicator disposed at an exterior surface of thehousing, the indicator being operable to track movement of the plungerwithin the bore of the reservoir when the proximity sensor is in thesecond sensor state and not being operable to track movement of theplunger within the bore of the reservoir when the proximity sensor is inthe first sensor state.
 34. The on-body injector of claim 33, whereinmoving the proximity sensor from the second sensor state to the firstsensor state decouples the indicator from the plunger such that theindicator does not track movement of the plunger within the bore of thereservoir.
 35. An on-body injector comprising: a reservoir including abore having a first end and a second end, and a plunger assemblyincluding a plunger moveable within the bore between the first andsecond ends and a plunger arm attached to the plunger; a cannula havingan operational state wherein the cannula is connected in fluidcommunication with the reservoir; a drive coupled to the plungerassembly to move the plunger between the first and second ends formoving a drug product out of the reservoir and through the cannula; ahousing, wherein the reservoir, the cannula, and the drive are disposedat least partially within the housing; a proximity sensor operablycoupled to move relative to the housing, the proximity sensor having afirst sensor state wherein the proximity sensor extends from the housingand a second sensor state wherein the proximity sensor is retractedtoward the housing relative to the first sensor state; a gear trainincluding at least one gear that is moveable into and out of engagementwith the plunger arm; and an indicator mechanically coupled to theplunger arm via the at least one gear when the proximity sensor is inthe second sensor state, the proximity sensor being coupled to the atleast one gear to move the at least one gear out of engagement with theplunger arm and mechanically decouple the indicator from the plunger armwhen the proximity sensor is in the first sensor state.
 36. An on-bodyinjector comprising: a reservoir including a bore having a first end anda second end, and a plunger assembly including a plunger moveable withinthe bore between the first and second ends; a volume of a drug productdisposed in the reservoir, the drug product comprising a granulocytecolony-stimulating factor (G-CSF); a cannula having an operational statewherein the cannula is connected in fluid communication with thereservoir; a drive coupled to the plunger assembly to move the plungerbetween the first and second ends for moving the drug product out of thereservoir and through the cannula; a housing, wherein the reservoir, thecannula, and the drive are disposed at least partially within thehousing; a proximity sensor operably coupled to move relative to thehousing, the proximity sensor having a first sensor state wherein theproximity sensor extends from the housing and a second sensor statewherein the proximity sensor is retracted toward the housing relative tothe first sensor state; an indicator selectively coupled to the plungerassembly when the proximity sensor is in the second sensor state andselectively de-coupled from the plunger assembly when the proximitysensor is in the first sensor state, wherein the indicator ismechanically coupled to the plunger assembly when the proximity sensoris in the second sensor state; and wherein the plunger assemblycomprises a plunger arm attached to the plunger, the indicator beingselectively mechanically coupled to the plunger arm through a gear trainhaving at least one gear that is moveable into and out of engagementwith the plunger arm, and the proximity sensor is coupled to the atleast one gear to move the at least one gear out of engagement with theplunger arm and decouple the indicator from the plunger arm with theproximity sensor in the first sensor state.